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Biomedical subjects

M Barbieri

Publications and source records attributed to M Barbieri.

At least 73 records · Page 4Linked to original sources
PubMed2000

Elevated plasma fatty acid concentrations stimulate the cardiac autonomic nervous system in healthy subjects.

BACKGROUND: Fatty acids have been shown to stimulate the sympathetic nervous system in rats. Power spectral analysis of heart rate variability (HRV) is a safe and useful tool with which to evaluate cardiac autonomic nervous system (ANS) activity. Whether changes in plasma fatty acid concentrations affect the sympathetic nervous system or HRV in humans is unknown. OBJECTIVE: We investigated the possible changes in HRV after a significant increase in plasma fatty acid concentration. DESIGN: Subjects were randomly assigned to receive an infusion of lipid emulsion (10% triacylglycerol emulsion for 180 min) + heparin (a bolus of 200 U followed by 0.2 U*min(-)(1)*kg body wt(-)(1); n = 20) or 0.9% NaCl (for 180 min; n = 10). RESULTS: Lipid emulsion + heparin infusion was associated with a rise in plasma epinephrine and norepinephrine concentrations. The rise in plasma fatty acid concentration was associated with a significant decline in the RR interval (P: < 0.03) and in total power (P: < 0.03). Analysis of the different components of HRV showed that lipid emulsion + heparin infusion stimulated low- frequency (LF) components (P: < 0.03 at the second hour and P: < 0. 01 at the third hour) and inhibited high-frequency (HF) components (P: < 0.03 at the second and third hours). Consequently, the LF-HF ratio was significantly stimulated (P: < 0.03 at the second hour and P: < 0.01 at the third hour). Such results persisted, although attenuated, when the study was repeated in association with a propranolol infusion (n = 8). CONCLUSION: Elevated plasma fatty acid concentrations may stimulate cardiac autonomic nervous system activity.

Adult↗
PubMed2000

Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

Adult↗
PubMed2000

Chronic vitamin E administration improves brachial reactivity and increases intracellular magnesium concentration in type II diabetic patients.

Vascular disease accounts for the majority of the clinical complications in diabetes mellitus. As an exaggerated oxidative stress degree has been postulated as the link between diabetes mellitus and endothelial function, a possible positive effect of plasma vitamin E (Vit.E) administration on brachial reactivity could be postulated. Our study aims at investigating the possible effect of chronic Vit.E administration on brachial reactivity, oxidative stress indexes, and intracellular magnesium and calcium content in type II diabetic patients free of diabetic complications. Forty adult, type II diabetic patients were enrolled in the study, which was deigned as a double blind, randomized vs. placebo trial. At baseline all patients underwent the following tests: 1) anthropometric and metabolic examinations, 2) evaluation of oxidative stress indexes, 3) intracellular magnesium and calcium measurements, and 4) determination of arterial compliance and distensibility. Then, all patients were randomly assigned to Vit.E treatment at a dose of 600 mg/day (Evion Forte; n = 20) or placebo (n = 20) over 8 weeks. At the end of this treatment period, a complete reevaluation of the patients was made. Vit.E treatment was associated with a significant improvement in the percent change in brachial artery diameter (P<0.03) and oxidative stress indexes (P< 0.005). In the Vit.E group, the percent change in brachial artery diameter correlated positively with the percent change in oxidative stress indexes (oxidized/reduced glutathione, Trolox-equivalent antioxidant capacity, thiobarbituric acid reaction products, lipid peroxides) and intracellular cation content (magnesium and calcium). After adjustment for age, sex, body mass index, and wait/hip ratio, all of these correlations remained significant (P<0.03 for all). Furthermore, adjusting for glycosylated hemoglobin, plasma total cholesterol, and homeostatic model index, brachial artery diameter was still correlated with the percent change in oxidative stress indexes (P<0.04 for all). Nevertheless, the relationship between the percent change in brachial artery diameter and oxidative stress indexes was no longer significant after adjustment for intracellular Mg and Ca2+. In conclusion, our study demonstrates that chronic administration of Vit.E improves brachial artery reactivity in patients with type II diabetes mellitus. Such an effect seems mediated by a reduction in oxidative stress and a regulation of intracellular calcium and magnesium contents.

Blood Glucose↗
PubMed2000

Adequate timing of fetal ultrasound to guide metabolic therapy in mild gestational diabetes mellitus. Results from a randomized study.

BACKGROUND: Ultrasound assessment of abdominal circumference early in the third trimester had been proposed to introduce insulin therapy in order to prevent fetal overgrowth in women with mild gestational diabetes mellitus. The purpose of this study was to investigate adequate weeks gestation timing for testing this parameter. METHODS: One hundred and forty-one women were included in a randomized trial. Seventy-three women were evaluated at both 28 and 32 weeks gestation whereas 68 women were investigated only at 32 weeks gestation. In both groups, insulin therapy was promptly started when abdominal circumference exceeded the 75th percentile. Macrosomic rates were compared using the Fisher's exact test. RESULTS: Twenty-nine women whose fetal abdominal circumference exceeded the 75th percentile were considered eligible for insulin therapy. In this group, we observed a statistically significant increase in the percentage of macrosomic infants born from women whose ultrasound abdominal circumference assessment was performed only at 32 weeks gestation when compared to women evaluated at both 28 and 32 weeks gestation (71.43% vs 33.33%, p<0.05). CONCLUSIONS: Our results support the need for fetal ultrasound at 28 weeks gestation to direct metabolic therapy since insulin administration introduced after 32 weeks gestation has a poor effect on fetal growth.

Abdomen↗
PubMed2000

Acetazolamide opens the muscular KCa2+ channel: a novel mechanism of action that may explain the therapeutic effect of the drug in hypokalemic periodic paralysis.

Acetazolamide is a thiazide derivative clinically used in skeletal muscle disorders related to altered K+ homeostasis such as the periodic paralyses. The mechanism of action responsible for the therapeutic effects of the drug is still unknown, however. In the present work, we investigated the mechanism of action of acetazolamide in the K-deficient diet rat, an animal model of human hypokalemic periodic paralysis (hypoPP). The in vivo administration of 2.8- and 5.6-mg/kg(-1)/day(-1) concentrations of acetazolamide to K-deficient diet rats prevented paralysis and depolarization of the fibers induced by insulin. In the acetazolamide-treated animals, intense sarcolemma Ca2+-activated K+ channel (KCa2+) activity was recorded. Acetazolamide also restored the serum K+ levels to control values. The concentrations of acetazolamide needed to enhance the KCa2+ current by 50% in vitro were 6.17 and 4.01x10(-6) M at -60 and +30 mV of membrane potentials, respectively. In normokalemic animals, the thiazide derivative enhanced the KCa2+ current with similar efficacy. Our data demonstrate that the therapeutic effects of acetazolamide in the K-deficient diet rats and possibly in human hypokalemic periodic paralysis patients can be mediated by activation of the KCa2+ channel.

Acetazolamide↗
PubMed2000

[Female sexuality: understanding its significance].

The present qualitative study with a phenomenological focus aimed at understanding the meaning of female sexuality to women who participate in the activities of an orientation group about this subject, organized by a family planning service. Through the analysis of the participants speeches and phenomenological reduction, authors found the central subject: Living sexuality. Results allowed authors to learn a little more on this subject, especially considering that women who took part in this group aimed at solving their problem as they believed they had sexual disorders. However, this fact was demystified, enabling them to understand that they have problems in living their sexuality.

Attitude to Health↗
PubMed1999

Electrophysiological actions of N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazola mine (R56865) on CA1 neurons of the rat hippocampal slice during hypoxia.

The electrophysiological effects of N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine (R56865), a drug which protects heart cells from ischemia-induced arrhythmias, was studied on intracellularly-recorded CA1 neurons of the rat hippocampal slice under normal or hypoxic conditions. On normoxic cells R56865 (1 microM) reduced firing accommodation without changing passive membrane properties, spike characteristics or synaptic transmission. On hypoxic cells R56865 selectively reduced the amplitude of hypoxia-induced membrane depolarization and partly counteracted the depression of synaptic transmission evoked by Schaffers collateral stimulation. Despite its influence on repetitive firing properties, R56865 might be useful to limit the extent of cellular depolarizing responses to hypoxia.

Animals↗
PubMed1999

Mean arterial blood pressure and serum levels of the molar ratio of insulin-like growth factor-1 to its binding protein-3 in healthy centenarians.

OBJECTIVE: Healthy centenarians have a greater molar ratio of plasma insulin-like growth factor-1 to insulin-like growth factor binding protein-3 than that of aged subjects. We investigated the question of whether differences in mean arterial pressure and in this plasma ratio were related in healthy centenarians. SUBJECTS AND METHODS: We studied 52 subjects in total, 30 aged subjects (70-99 years) and 22 healthy centenarians (> 100 years) to determine differences in mean arterial pressure, endothelial function and intracellular cation levels. RESULTS: In the healthy centenarians, the molar ratio of fasting plasma insulin-like growth factor-1 to its binding protein-3 was significantly correlated with mean arterial pressure (r = -0.66, P < 0.001). Baseline (19.3 +/- 1.5 versus 27.6 +/- 2.2 mumol/l, P < 0.05) and L-arginine-stimulated percentage increases in the plasma total nitrate: nitrite ratio (67 +/- 3.4 versus 48 +/- 4.5%, P < 0.03) were greater in the healthy centenarians than in the aged subjects. An L-arginine bolus elicited an increase in forearm blood flow which was correlated with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.79, P < 0.001) and with the fasting erythrocyte magnesium concentration (r = 0.80, P < 0.001) in healthy centenarians. Both correlations remained significant (P < 0.01) after adjustment for sex, body mass index and the waist: hip ratio. Moreover, the fasting plasma molar ratio of insulin-like growth factor-1 to its binding protein-3 was correlated with the percentage increase in forearm blood flow (r = 0.59, P < 0.005) and with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.54, P < 0.009) in healthy centenarians. The centenarians had higher baseline total erythrocyte magnesium and lower calcium concentrations than the aged subjects. The addition of insulin growth factor-1 to the incubation medium increased the total intracellular erythrocyte magnesium content and decreased the calcium content in both groups of subjects. Nevertheless, the percentage increase in total erythrocyte magnesium (33 +/- 3.8 versus 12 +/- 3.4%, P < 0.03) and decline in intracellular calcium (17 +/- 2.8 versus 8 +/- 3.1%, P < 0.02) concentrations were greater in the healthy centenarians than the aged subjects. CONCLUSION: In healthy centenarians, insulin-like growth factor-1 may preserve endothelial function and modulate the intracellular cation content, thus contributing to a lower mean arterial pressure than that in aged subjects.

Aged↗
PubMed1999

Low plasma insulin-like growth factor-1 concentrations predict worsening of insulin-mediated glucose uptake in older people.

OBJECTIVE: The relationship among insulin action, advancing age, and insulin like growth factor-1 (IGF-1) is poorly understood. To gain further insight, the predictive role that low plasma IGF-1 concentration may have on insulin- mediated glucose uptake in older persons was investigated. DESIGN: The study was designed as a longitudinal, observational trial. PARTICIPANTS: Fifty-eight healthy aged (73.1+/-9.4 years) subjects (31 males/27 females) were followed up for 12 months. MEASUREMENTS: At baseline and at the end of the follow-up, insulin-mediated glucose uptake was assessed by euglycemic glucose clamp and plasma total IGF-1 and IGF-binding protein 3 (IGF-BP-3) in each subject, and concentrations were determined. RESULTS: At baseline, plasma IGF-1 concentrations correlated with whole body glucose uptake (WBGD) (r = 0.39, P < .003), insulin-stimulated glucose oxidation (GOX) (r = 0.35, P < .009), and non-oxidative glucose metabolism (r = 0.37, P < .007). Such correlations were also independent of age, sex, body fat, and waist/hip ratio. Fasting plasma total IGF-1 concentrations (84+/-56 vs 63+/-44 microg/L, P < .040), plasma IGF-1/IGF-BP3 molar ratio (0.13+/-0.05 vs 0.10+/-0.03 P < .050), and WBGD (34.8+/-5.0 vs 23.1+/-4.6 micromol/kg x min, P < .010) were more elevated at baseline than at the end of the follow-up. Low baseline fasting plasma IGF-1 concentration (RR = 1.5, 95%CI = 1.3-1.7) and plasma IGF-1/IGFBP-3 molar ratio (RR = 1.4, 95% CI = 1.3-1.8) predicted a decline in WBGD. The predictive role of plasma IGF-1 on age-related decline in WBGD was independent of age, sex, body fat, waist/hip ratio, and degree of physical activity (model 1), or of fasting plasma free fatty acid and triglyceride concentrations, LDL/HDL ratio, and basal adjusted respiratory quotient (model 2). Finally, low plasma IGF-1 concentration predicts a decline in WBGD independent of body fat, free fatty acids, waist/hip ratio, and basal adjusted respiratory quotient (model 3). CONCLUSION: Our study demonstrates that fasting plasma IGF-1 concentration may have a modulatory role on insulin action in older people. This finding might prompt an evaluation of the direct effect of IGF-1 administration on insulin sensitivity in older adults.

Adipose Tissue↗
PubMed1999

Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). PATIENTS AND METHODS: Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. RESULTS: Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. CONCLUSION: The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.

Adult↗
PubMed1999

Baseline heart rate variability in healthy centenarians: differences compared with aged subjects (>75 years old).

Healthy centenarians have better anthropometric, endocrine, metabolic and immunological parameters than aged subjects (>75 years old). Heart rate variability (HRV) has been demonstrated to be a good index of the cardiac autonomic nervous system. It is not known whether there are any differences in cardiac autonomic nervous system activity between aged subjects and healthy centenarians. It is possible that differences in cardiac autonomic nervous system activity could represent one of a cluster of factors explaining the extreme survival of centenarians. Thus we aimed to answer the following question: is there any difference in baseline HRV parameters between aged subjects and healthy centenarians? Therefore power spectral analysis of HRV at baseline was investigated in 25 aged subjects (age > or = 75 years) and 30 healthy centenarians (age > or = 0 years). Anthropometric measurements were made in all subjects, fasting blood samples were drawn for metabolite determinations, and HRV was determined. Independent of age, gender, body mass index and fasting plasma noradrenaline and free 3,3',5-tri-iodothyronine concentrations, healthy centenarians had lower basal values for total power (1318+/-546 compared with 1918+/-818 ms(2); P<0.01) and the low-frequency component (33+/-21 compared with 50+/-11 normalized units; P<0.03) and a higher value for the high-frequency component (77+/-15 compared with 61+/-18 normalized units; P<0.05) than aged subjects. Consequently, the low-frequency/high-frequency ratio (0.43+/-0.07 compared with 0.91+/-0.05; P<0.02) was also lower in the healthy centenarians than in the aged subjects. Our study demonstrates that the basal low-frequency/high-frequency ratio, an indirect index of cardiac sympathovagal balance, is lower in healthy centenarians than in aged subjects.

Aged↗
PubMed1999

Primary and secondary prevention of atherosclerosis: is there a role for antioxidants?

Elevated plasma free radical concentration (expression of enhanced oxidative stress) is related to different pathophysiological conditions such as ageing, cancer and diabetes. Nevertheless, even in healthy subjects a rise in plasma free radicals is due to hyperglycaemia, elevated free fatty acids and hyperinsulinaemia. Once elevated oxidative stress occurs, accelerated atherosclerosis may be present. Thus, antioxidants might potentially be useful in preventing or delaying the development of atherosclerosis. Several epidemiological studies have provided conflicting results, whereas interventional studies have demonstrated that antioxidant administration at pharmacological doses is useful for secondary prevention of atherosclerosis. The role of antioxidants in diabetic patients is still debatable, and it is too early to suggest this means for the prevention of atherosclerosis. Concerning trace elements, several studies have indicated that iron, copper, zinc and selenium may play a role in the pathogenesis of atherosclerosis. Nevertheless, only future longitudinal studies can provide a final response. In conclusion, the whole body of studies to date clearly demonstrates that antioxidants may be useful for secondary prevention of coronary heart disease.

Antioxidants↗
PubMed1998

Effects of mexiletine on ATP sensitive K+ channel of rat skeletal muscle fibres: a state dependent mechanism of action.

1. The effects of mexiletine were evaluated on the ATP-sensitive K+ channel (K(ATP)) of rat skeletal muscle fibres using patch clamp techniques. The effects of mexiletine were studied on macropatch currents 20 s (maximally activated), 8 min (early stage of rundown) and 15 min (late stage of rundown) after excision in the absence or in the presence of internal ADP (50-100 microM) or UDP (500 microM). In addition, the effects of mexiletine were tested on single channel. 2. In the absence of ADP and UDP, mexiletine inhibited the current through maximally activated channels with an IC50 of -5.58+/-0.3 M. Nucleoside diphosphates shifted the current versus mexiletine concentration relationship to the right on the log concentration axis. UDP (500 microM) was more efficacious than ADP (50-100 microM) in this effect. 3. At the early stage of rundown, the sensitivity of the channel to mexiletine was reduced and nucleoside diphosphates, particularly UDP, antagonized the effect of mexiletine. At the late stage of rundown, mexiletine did not affect the currents. 4. At the single channel level, 1 microM mexiletine reduced the mean burst duration by 63% and prolonged the arithmetic mean closed time intervals between the bursts of openings without altering the open time and closed time distributions. Mexiletine did not affect the single channel conductance. 5. These results show that in skeletal muscle, mexiletine is a state-dependent K(ATP) channel inhibitor which either acts through the nucleotide binding site or a site allosterically coupled to it.

Adenosine Diphosphate↗
PubMed1998

Diagnostic evaluation of a synthetic peptide derived from a novel antigen B subunit as related to other available peptides and native antigens used for serology of cystic hydatidosis.

A synthetic peptide (GU4) derived from an antigen B (AgB) subunit was serologically compared with crude antigen (HCFA); immunopurified AgB and antigen 5 (Ag5), and two other synthetic peptides, for diagnosis of human cystic hydatidosis. GU4 was derived from the sequence of AgB/2, the novel AgB subunit described by us. The other two peptides: 65 (AgB mimotope) and 89-122 (Ag5 mimotope), were described by others. Antigens B and 5 showed higher diagnostic sensitivity than corresponding peptides. All sera reacting with peptides 89-122 and GU4 also reacted with 65. The latter provided three to four times higher sensitivity than the former two peptides, but 30% lower specificity. The diagnostic efficiency of AgB (82%) was higher than those of Ag5 (74%) and HCFA (71%). Interestingly, 89-122 only reacted with hydatid sera, some of which did not react with AgB. Considering positive those reacting with 89-122 or AgB, sensitivity increases from 77% (with AgB) to 82% (combined), while specificity is the same as with AgB (86%). Our results suggest that hydatid serology may be improved by: a) combining several defined antigens (including synthetic peptides), b) design of new E. granulosus-specific mimotopes, which react with the false negative sera (16/90; 18%).

Animals↗