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A De Gaetano

Publications and source records attributed to A De Gaetano.

At least 19 recordsLinked to original sources
PubMed2006

Within-patient variation of the pharmacokinetics of subcutaneously injected biphasic insulin aspart as assessed by compartmental modelling.

AIMS/HYPOTHESIS: Pharmacokinetics of s.c. administered insulin preparations have been widely studied, mostly using descriptive measures such as AUC, time to peak, or the peak plasma concentration. Several compartmental modelling studies of single-bolus s.c. insulin pharmacokinetics have also appeared, with contrasting results regarding the feasibility of insulin pharmacokinetics modelling and the appropriate level of detail for such models. In this paper, we used compartmental models to study the pharmacokinetics of biphasic insulin aspart administered by multiple s.c. injections. The main objective was to assess the magnitude of the inter-and intra-subject variation in the kinetics. MATERIALS AND METHODS: Analyses were performed on 24-h serum insulin concentrations measured in 20 type 1 diabetes subjects given three daily s.c. injections of biphasic insulin aspart. RESULTS: Preliminary analysis of the AUC:dose ratio showed that the apparent kinetics are not constant throughout the three daily injections of the compound. A simple and robust compartmental model was shown to be appropriate for interpreting the observations, provided that one of its parameters (the first-order rate constant for transfer from the s.c. depot to plasma) is allowed to vary between injections. CONCLUSIONS/INTERPRETATION: Population estimates of the chosen model show that intra-subject variations between injections is of the same order of magnitude as inter-subject variation, partially explaining the difficulties encountered when individually tailoring intensified insulin therapy. We conclude that the explicit consideration of a rather simple kinetic model will allow better experimental designs in the future study of s.c. insulin preparations.

Area Under Curve↗
PubMed2005

Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.

OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. METHODS: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1 coding region was sequenced from genomic DNA; cDNA was analyzed in selected cases. RESULTS: Homozygous pathogenic mutations were identified in 4 of 90 Italian sporadic cases, including the novel Gln456Stop mutation; single heterozygous truncating or missense mutations were found in another 4 Italian sporadic cases, including two novel mutations, Pro196Leu and Gln456Stop. Pathogenic mutations were not identified in the familial cases. Novel (Gln115Leu) and known polymorphisms were identified with similar frequency in cases and controls. In cases carrying single heterozygous mutation, cDNA analysis detected no additional mutations, and revealed a major pathogenic effect at mRNA level for the mutant C1366T/Gln456Stop allele. All patients with homozygous mutations had very early disease onset, slow progression, and excellent response to l-dopa, including, in some, symmetric onset, dystonia at onset, and sleep benefit, resembling parkin-related disease. Phenotype in patients with single heterozygous mutation was similar, but onset was later. CONCLUSIONS: PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.

Adolescent↗
PubMed2003

Sublethal effect of a weak intermittent magnetic field on the development of Xenopus laevis (Daudin) tadpoles.

In three repeated experiments with three different litters of Xenopus laevis (Daudin) tadpoles, three cohorts were reared in an aquarium under the "saw-tooth" magnetic field produced by a television set. Their maturation times are compared with those of three corresponding control cohorts grown in an unexposed aquarium. In the exposed aquarium, the magnetic field amplitude was less than 25 microT and the frequency in the extremely-low-frequency and very-low-frequency wavebands. Neither the exposed nor the unexposed cohorts suffered significant mortality and malformations. However, the exposed tadpoles took about 5 days more than the unexposed ones to reach metamorphosis. The differences in mean maturation times between the exposed and control cohorts were extremely significant (P < 0.001). The results show that a biological population can suffer a sublethal effect when exposed to the magnetic field of a TV set for a long time in the course of juvenile life stages, and that this effect can consist of a delay in reaching the adult stage.

Animals↗
PubMed2003

An endogastric capsule for measuring tumor markers in gastric juice: an evaluation of the safety and efficacy of a new diagnostic tool.

BACKGROUND: In gastric juice, high levels of the carcinoembryonic antigen (CEA) and the carbohydrate antigen 19-9 (CA 19-9) have been found to correlate with precancerous lesions and gastric cancer. So far, sampling of gastric juice has required upper endoscopy. In place of this invasive procedure, we investigated a new tool for the quantitation of tumor markers in gastric juice. MATERIALS AND METHODS: The study population consisted of healthy controls and consecutive subjects with suspected gastric cancer or dyspepsia/epigastric distress. Patients were asked to swallow a small gelatine capsule (14 mm in length and 5 mm in diameter) containing a pierced plastic cover and surrounding a piece of absorbent paper. The capsule was left in the gastric cavity for 60 min to allow saturation of the absorbent paper with gastric juice. A 45-50 cm length of nylon thread connected to the inner capsule was used to remove the device from the gastric cavity. After processing the absorbent paper for radioimmunoassay, CEA and CA 19-9 levels were correlated to the findings of upper endoscopy and biopsies of gastric mucosa or suspected lesions. RESULTS: The endogastric capsule did not cause any side-effects and 62 participants were fully compliant to the procedure. Assessable gastric juice samples were taken from 23 patients with gastric cancer, 15 patients with intestinal metaplasia or dysplasia, 12 patients with gastritis and 12 controls without gastric diseases. In the 12 samples of gastric juice from control patients, mean values of CEA and CA 19-9 were 1.1 +/- 0.9 ng/ml and 16 +/- 7.5 ng/ml, respectively. The mean levels of both markers were found to increase according to the severity of gastric lesions and in patients with cancer, mean CEA and CA 19-9 levels were 513 +/- 627 ng/ml and 545 +/- 510 ng/ml, respectively. Patients with precancerous lesions and cancer showed higher levels of CEA and CA 19-9 than patients with normal findings or gastritis (P <0.001). CONCLUSIONS: The endogastric capsule is a simple, non-invasive tool for the measurement of CEA and CA 19-9 levels in gastric juice. These values may discriminate between normal or minor pathologic changes and precancerous lesions or carcinomas. Further investigations are warranted, since this may represent a new method for gastric cancer screening.

Adolescent↗
PubMed2002

Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients.

Ifosfamide and cisplatin cause urinary loss of carnitine, which is a fundamental molecule for energy production in mammalian cells. We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients. Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry. Patients were excluded if they had anaemia or other conditions thought to be causing asthenia. Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire. Treatment consisted of oral levocarnitine 4 g daily, for 7 days. Fifty patients were enrolled; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients. In the whole group, baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 (+/-6.4; standard deviation) and the mean plasma carnitine value was 20.9 microM (+/-6.8; standard deviation). After 1 week, fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 (+/-5.4; standard deviation) (P<.001). All patients achieved normal plasma carnitine levels. Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy. In selected patients, levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue. This compound deserves further investigations in a randomised, placebo-controlled study.

Acetylcarnitine↗
PubMed2002

Computing DIT from energy expenditure measures in a respiratory chamber: a direct modeling method.

The possibility of computing Diet Induced Thermogenesis (DIT) is an important feature of metabolic investigations. However, methodological problems have affected the determination of DIT in the indirect calorimetric chamber. DIT has been commonly estimated by regressing energy expenditure on a measure of physical activity. Although used for many years as the only feasible approach to calculate DIT in a respiratory chamber, this traditional method has been criticized because of an apparent underestimation of the DIT, but no alternative method has been suggested so far. The present work proposes to estimate DIT directly by means of a mathematical model. This approach also allows to simultaneously estimate other parameters, namely resting energy expenditure (REE), physical activity (PA) and physical exercise (PE).

Adult↗
PubMed2000

Mathematical modelling of the intravenous glucose tolerance test.

Several attempts at building a satisfactory model of the glucose-insulin system are recorded in the literature. The minimal model, which is the model currently mostly used in physiological research on the metabolism of glucose, was proposed in the early eighties for the interpretation of the glucose and insulin plasma concentrations following the intravenous glucose tolerance test. It is composed of two parts: the first consists of two differential equations and describes the glucose plasma concentration time-course treating insulin plasma concentration as a known forcing function; the second consists of a single equation and describes the time course of plasma insulin concentration treating glucose plasma concentration as a known forcing function. The two parts are to be separately estimated on the available data. In order to study glucose-insulin homeostasis as a single dynamical system, a unified model would be desirable. To this end, the simple coupling of the original two parts of the minimal model is not appropriate, since it can be shown that, for commonly observed combinations of parameter values, the coupled model would not admit an equilibrium and the concentration of active insulin in the "distant" compartment would be predicted to increase without bounds. For comparison, a simple delay-differential model is introduced, is demonstrated to be globally asymptotically stable around a unique equilibrium point corresponding to the pre-bolus conditions, and is shown to have positive and bounded solutions for all times. The results of fitting the delay-differential model to experimental data from ten healthy volunteers are also shown. It is concluded that a global unified model is both theoretically desirable and practically usable, and that any such model ought to undergo formal analysis to establish its appropriateness and to exclude conflicts with accepted physiological notions.

Adult↗
PubMed2000

Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides.

A close relationship between elevated plasma free fatty acid (FFA) levels and insulin resistance is commonly reported in obese subjects. The aim of the present study was to evaluate the role of intramuscular triglyceride (mTG) and FFA levels in insulin sensitivity in 30 nondiabetic normal-weight or obese subjects (18 with body mass index [BMI] = 21.8 +/- 3.3 kg/m2 and 12 with BMI = 34.6 +/- 2.7 kg/m2) who underwent minor abdominal surgery. Body composition was estimated by isotopic dilution, substrate oxidation by indirect calorimetry, and whole-body glucose uptake by euglycemic-hyperinsulinemic clamp (EHC). Glucose uptake (M) value negatively correlated with the MTG level (R2 = -.56, P < .0001), which was increased in obese patients (11.6 +/- 2.2 v 6.2 +/- 1.4 micromol/g wet weight muscle tissue, P < .0001). The TG fatty acid profile was significantly different in the 2 groups: an increased concentration of saturated fat was present in obese patients (unsaturated to saturated ratio, 1.89 +/- 0.40 v2.19 +/- 0.07, P < .0001). Stepwise linear regression analysis of total mTGs and palmitic and oleic fractions on the M value showed that only TGs and palmitic acid were significantly related to glucose uptake (R2 = .66, P < .0001). Furthermore, among the other anthropometric variables, only the BMI was significantly correlated with MTGs (R2 = .71, P < .0001). In conclusion, not only the MTG concentration but also the FFA pattern seems to affect insulin-mediated glucose uptake. A pivotal role might be played by a high saturated fatty acid content in the TGs.

Adult↗
PubMed2000

Botulinum toxin injected in the gastric wall reduces body weight and food intake in rats.

BACKGROUND: Botulinum toxin is a powerful, long-acting inhibitor of muscular contractions in both voluntary and smooth muscle. It acts by blocking the release of the neurotransmitter acetylcholine. In the stomach, propulsive contractions of the antrum are necessary for the gastric contents to pass into the duodenum. AIMS: To investigate whether intramuscular injections of botulinum toxin type A into the gastric antrum of rats would cause a reduction in food intake and hence body weight, by inhibition of gastric emptying. MATERIALS AND METHODS: This was a prospective, randomized, 3-way parallel group study in rats. The first group was anaesthetized, laparotomized and given 20 U of botulinum toxin type A by intramuscular injection into the gastric antrum (botulinum toxin type A group, n=14). The second group was anaesthetized, laparotomized and injected with saline (sham group, n=14) and the third group did not have any intervention (control group, n=5). Food intake was measured daily for 7 weeks and body weight was measured daily for 10 weeks. RESULTS: There was a significant difference in loss of body weight between the two treated groups (14.0 +/- 8.2% botulinum toxin type A group, 4.4 +/- 2.7% sham group; P < 0.001). Further, the time to reach the weight nadir was significantly longer in the botulinum toxin type A group (8.7 +/- 3.9 days) compared with the sham group (5.3 +/- 3.8 days; P < 0.04). There were no significant differences between the sham and control groups for any of the body weight parameters. The minimum dietary intake was significantly lower in the botulinum toxin type A group than in the sham group (37.8 +/- 21.8% of the basal value in the botulinum toxin type A group, vs. 65.5 +/- 32.0 in the sham group, P < 0.05). In addition, the time to reach the nadir was significantly prolonged (8.2 +/- 3.5 days, botulinum toxin type A group vs. 4.9 +/- 1.7 days, sham group, P < 0.001). CONCLUSIONS: The parallel reduction of body weight and food intake in botulinum toxin type A treated animals is consistent with a long lasting inhibition of the antral pump. This is probably due to slowed gastric emptying leading to early satiety. Patients with morbid obesity might benefit from endoscopic injections of botulinum toxin type A into the stomach wall.

Animals↗
PubMed2000

Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients.

Little information is available in the literature on the effect of L-carnitine to improve glucose disposal in healthy control subjects and type 2 diabetic patients. No data are reported on the pharmacological properties of acetyl-L-carnitine (ALC) in type 2 diabetes mellitus. The present study evaluates glucose uptake and oxidation rates with either ALC or placebo administration in 18 type 2 diabetic patients. On different days, each patient received both a primed-constant infusion of ALC (5 mg/kg body weight [BW] priming bolus and either 0.025, 0.1, or 1.0 mg/kg BW/min constant infusion) and a comparable placebo formulation. During the infusion period, continuous indirect calorimetric monitoring and a euglycemic-hyperinsulinemic clamp (EHC) study were performed. The total end-clamp glucose tissue uptake (M value) was significantly increased by the administration of ALC (from 3.8 to 5.2 mg/kg/min, P = .006), and the dose dependence of this effect reached borderline statistical significance (P = .037). The increase in the M/I ratio was also highly significant after ALC administration (from 3.9 to 5.8 x 10(-2) mg/kg/min/(microUI/mL, P < .001), while no statistically significant effect was attributable to the different dosages. The increase in the M value was related to increased glucose storage (highly significant effect of ALC) rather than increased glucose oxidation (no statistical significance). In conclusion, the effect of ALC on glucose disposal has no relationship to the amount administered. This could be due to an effect of ALC on the enzymes involved in both the glycolytic and gluconeogenetic pathways, and a possible reversibility of glycogen synthase inhibition in diabetic subjects.

Acetylcarnitine↗
PubMed2000

Changes in body composition, substrate oxidation, and resting metabolic rate in adult celiac disease patients after a 1-y gluten-free diet treatment.

BACKGROUND: The incidence of celiac disease has been on the rise in both Europe and the United States. Celiac disease patients are at high risk of undernutrition because of nutrient malabsorption. OBJECTIVE: The aim of the present study was to evaluate changes in body composition and energy metabolism in a group of patients with celiac disease before and after consumption of a gluten-free diet (GFD). DESIGN: Body composition (by anthropometry and isotopic dilution), resting metabolic rate (RMR), and substrate oxidation rates (by indirect calorimetry) were assessed in 39 adult celiac disease patients (16 men and 23 women) with a mean (+/-SD) age of 29. 9 +/- 7.6 y, weight of 58.3 +/- 6.6 kg, and percentage body fat of 20.1 +/- 6.7%, and in 63 (29 men and 34 women) age- and height-matched control subjects (age: 33.2 +/- 8.1 y; weight: 66.8 +/- 6.6 kg; and percentage body fat: 25.4 +/- 3.7%). Celiac disease patients were studied twice, at diagnosis and 1 y after treatment with a GFD. RESULTS: Before treatment, celiac disease patients had a lower body weight (P < 0.05) and a higher carbohydrate oxidation rate (P < 0.01) than did control subjects. Carbohydrate oxidation rates correlated positively with fecal lipid loss in untreated celiac disease patients (r = 0.80, P < 0.0001). After the GFD, percentage body fat was higher in celiac disease patients than in control subjects (P < 0.01), and lipid intakes tended to be higher than before treatment. CONCLUSIONS: This longitudinal study showed that the GFD treatment significantly increased body fat stores. Untreated patients preferentially utilized carbohydrates as a fuel substrate, probably as a consequence of both lipid malabsorption and a high carbohydrate intake, and lipid utilization increased with the restoration of the intestinal mucosa.

Adolescent↗
PubMed2000

Physiologic determinants of ventilator dependence in long-term mechanically ventilated patients.

To investigate the pathophysiologic mechanisms of ventilator dependence, we took physiologic measurements in 28 patients with COPD and 11 postcardiac surgery (PCS) patients receiving long-term mechanical ventilation during a spontaneous breathing trial, and in 20 stable, spontaneously breathing patients matched for age and disease. After 40 +/- 14 min of spontaneous breathing, 20 of 28 patients with COPD and all 11 PCS patients were judged ventilator-dependent (VD). We found that in the 31 VD patients tidal volume was low (VT: 0.36 +/- 0.12 and 0.31 +/- 0.08 L for COPD and PCS, respectively), neuromuscular drive was high (P(0.1): 5.6 +/- 1. 6 and 3.9 +/- 1.9 cm H(2)O), inspiratory muscle strength was reduced (Pdi(max): 42 +/- 12 and 28 +/- 15 cm H(2)O), and lung mechanics were abnormal, particularly PEEPi (5.9 +/- 3.0 cm H(2)O) and lung resistance (22.2 +/- 9.2 cm H(2)O/L/s) in COPD. The load/capacity balance was altered (Pdi/Pdi(max) and Ppl/Ppl(max) > 0.4) and the effective inspiratory impedance was high (P(0.1)/VT/TI >/= 10 cm H(2)O/L/s). Failure to wean occurred in patients with f/VT > 105 breaths/min/L and 56% of patients with COPD with f/VT < 80 breaths/min/L. Those who failed despite a low f/VT ( < 80 breaths/min/L) either showed ineffective inspiratory efforts, which artificially lowered f/ VT (n = 8), or did not increase breathing frequency (n = 5), but P(0.1) and P(0.1)/VT/TI were as high as in other VD patients. In the 31 VD patients, Pa(CO(2)) increased during the weaning trial (+12.3 +/- 8.0 mm Hg). We conclude that in the presence of a high drive to breathe, the imbalance between increased work load and reduced inspiratory muscle strength causes respiratory distress and CO(2) retention. Noninvasive measurements (breathing pattern, P(0.1), P(0.1)/ VT/TI) may give better insight into weaning failure useful in clinical decision-making, particularly in patients with COPD not showing rapid shallow breathing (56% in this study).

Aged↗
PubMed1999

Comparison of insulin response to intravenous glucose in healed myocardial infarction, in "cooled-off" unstable and stable angina pectoris, and in healthy subjects.

Fasting and postglucose hyperinsulinemia are recognized risk factors for acute coronary events. The insulin reactivity of patients with acute coronary syndromes, however, has not been carefully compared with that of patients with chronic stable angina. We used Bergman's minimal model to analyze the insulin response to intravenous glucose in 21 subjects: 8 patients with previous (>3 months) acute coronary syndrome but no effort-related angina; 6 patients with stable effort angina but no prior acute event; and 7 healthy controls. Diabetes mellitus, systemic hypertension, dyslipidemias, and obesity were excluded. All patients underwent coronary angiography. Insulin sensitivity, glucose effectiveness, and glucose tolerance were determined from insulin and glucose concentrations measured frequently up to 3 hours after a 0.33 g/kg intravenous glucose bolus. Patients with previous unstable angina or acute myocardial infarction had less extensive disease at angiography than patients with stable angina (p = 0.007). Both patient groups had higher basal and 180-minute insulinemia than controls (p <0.0007). However, patients with stable angina did not differ significantly from controls with regard to early and late insulinemic response to glucose. In contrast, patients with previous acute onset of ischemia had significantly greater 180-minute integrated insulinemia (p = 0.04) and reduced insulin sensitivity (p = 0.05) after the glucose challenge than did the stable angina group. These data suggest that patients with acute presentation of coronary artery disease, compared with patients with uncomplicated chronic stable angina, have an impaired insulin response to glucose despite less extensive coronary disease at angiography.

Analysis of Variance↗
PubMed1999

A new HPLC method for the direct analysis of triglycerides of dicarboxylic acids in biological samples.

Dicarboxylic acids (DA) are alternate lipid substrates recently proposed in parenteral nutrition. Two new derivatives of DA, a triglyceride of sebacic (TGC10) and one of dodecanedioic (TGC12) acid have been synthesised in order to reduce the amount of sodium given with the unesterified forms. The present paper describes a rapid and direct high-performance liquid chromatographic method (HPLC) for the analysis of these substances in both plasma and urine. Thirty-six male Wistar rats were rapidly injected with 64 mg of TGC10 or 53 mg of TGC12. The triglycerides and their products of hydrolysis were measured in plasma samples taken at different times. For the dose of 500 ng the intra-assay variations ranged from 6. 80+/-0.35% for TGC10 to 18.6+/-3.20% for TGC12 and the inter-assay variations were from 4.44+/-2.21% for TGC10 to 15.0+/-6.72% for TGC12. The detection limit for both triglycerides was 5 ng. This rapid and direct HPLC method could have practical implications in monitoring the concentration of both triglycerides and free forms of DA in biological samples of patients who might benefit from the administration of these substances during parenteral nutrition regimens.

Animals↗
PubMed1999

Multivariate identification of metabolic features in inflammatory bowel disease.

Weight loss and malnutrition are commonly reported in inflammatory bowel disease (IBD), but differences between Crohn's disease (CD) and ulcerative colitis (UC) patients have rarely been pointed out. In this regard, a sample of 102 consecutive patients with a diagnosis of either CD (n = 63, 33 males) or UC (n = 39, 25 males) based on previously reported clinical, morphologic, and histopathologic criteria were studied. Twenty-six anthropometric and metabolic variables were measured upon admission. Body composition was assessed by both anthropometry and bioimpedance measurements, and energy expenditure and substrate oxidation were assessed by indirect calorimetry. The data were subjected to principal-component analysis and to factor rotation to derive a set of a few basic independent descriptors of the metabolic features of each subject. Six descriptors were found to be responsible for greater than 86% of the total sample variability and to associate very well with mutually disjoint subsets of the original variables. The six summarizing factors are listed in order of decreasing percentage of explained variation (size 41.8%, fatness 17.9%, fuel 12.2%, shape 5.4%, energy 5.2%, and steroid 3.9%). CD and UC patients differed significantly with respect to fatness (CD lower, P = .004) and carbohydrate (CHO) fuel preference (CD lower, P = .030). Hence, CD patients showed a reduced fat mass (FM) compared with UC patients, and from a metabolic point of view, too, CD and UC are not superimposable. In fact, the lower CHO oxidation (CHOox) rate and consequent preferential lipid utilization found in CD patients may be taken into account as a contributing cause of lipid tissue wasting and in planning therapeutic enteral regimens.

Adolescent↗