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Biomedical subjects

G Bonetti

Publications and source records attributed to G Bonetti.

At least 19 recordsLinked to original sources
PubMed1999

Association between apolipoprotein(a) phenotypes and coronary heart disease at a young age.

OBJECTIVES: The purpose of this study was to investigate lipoprotein(a) [Lp(a)] levels and apolipoprotein(a) [apo(a)] phenotypes in relation to age of onset of coronary heart disease (CHD). BACKGROUND: Although Lp(a) levels have been extensively analyzed in relation to age of CHD, apo(a) phenotypes have not. METHODS: Three hundred and thirty-five consecutive CHD patients were enrolled and grouped according to their age of CHD onset (<45 years; 45 to 54 years; > or = 55 years). RESULTS: In each patient group Lp(a) levels were higher than in an age-matched control group, but among the patient groups no differences in Lp(a) levels were observed. Apolipoprotein(a) phenotype distributions showed significant differences between patients and age-matched control subjects. Among the patient groups the difference in percentage of subjects with two apo(a) isoforms of low molecular weight (MW) was highly significant (p < 0.001). Multivariate analysis showed that apo(a) phenotypes were the best predictors of early CHD (p < 0.000001). The age-specific odds ratios (ORs) of the presence of at least one apo(a) isoform of low MW for CHD declined with age; in particular apo(a) phenotypes had their highest predictive value in younger persons (OR: 14.62). The OR for the presence of two isoforms of low MW/presence of only isoforms of high MW was 40.88 in the younger age group, 27.17 in age group of 45 to 54 years and 15.83 in the older age group. CONCLUSIONS: The present article reports the first evidence of a strong independent association of apo(a) phenotypes with the age of onset of CHD. Thus, if our data are confirmed by larger studies, apo(a) phenotypes might be used together with Lp(a) levels as powerful genetic markers in assessing the actual risk of developing CHD at a young age.

Adult↗
PubMed1998

The altered plasma amino acid pattern is responsible for the paradoxical growth hormone response to the oral glucose tolerance test in liver cirrhosis.

OBJECTIVE: An increased basal growth hormone (GH) secretion and a parodoxical GH response to the oral glucose tolerance test (OGTT) have been reported in patients with liver cirrhosis. It has been suggested that the ratio between branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) (BCAA/ AAA ratio) may determine in part the brain concentration of the AAAs, since the BCAAs compete with the AAAs for entry across the blood-brain barrier, leading to the accumulation of false neurotransmitters such as octopamine and phenylethanolamine, which are able to stimulate GH secretion (via alpha 2-adrenergic stimulation). In this study we investigated the role of amino acids, particularly the BCAA/AAA ratio, in the paradoxical response of GH to the OGTT in patients with liver cirrhosis. PATIENTS AND DESIGN: Twelve non-diabetic patients with biopsy-proven cirrhosis of the liver underwent an OGTT. Three of the five patients with a paradoxical response of GH to the OGTT underwent a second oral glucose administration associated with an infusion of BCAA solution from -30 min until 180 min. RESULTS: During the OGTT, glucose and insulin levels increased from 4.8 +/- 0.2 to 9.6 +/- 0.7 mmol/l (P < 0.001) and from 18.8 +/- 2.6 to 104.4 +/- 13.8 mU/l (P < 0.005), respectively. GH levels increased from 8.6 +/- 2.6 to 22.4 +/- 10.8 mU/l although not significantly. Five patients had a paradoxical GH response to the OGTT. A negative correlation between serum GH values and BCAA/AAA ratio in the plasma at every time point of the OGTT was found. After co-administration of glucose and BCAA in three patients the BCAA/AAAs ratio increased, abolishing the paradoxical GH secretion. CONCLUSIONS: Our data suggest that in liver cirrhosis the altered BCAA/AAA ratio may influence the altered basal GH secretion and the paradoxical GH response to the OGTT, probably by an increase of adrenergic mediators in the brain. Moreover, the increase of BCAA/AAA ratio seems to be able to abolish the GH paradoxical response to the OGTT.

Adult↗
PubMed1998

Apolipoprotein(a) phenotypes and their predictive value for coronary heart disease: identification of an operative cut-off of apolipoprotein(a) polymorphism.

BACKGROUND: Apolipoprotein(a) isoforms of low-molecular weight are associated with coronary heart disease. However, because of the high number of apolipoprotein(a) isoforms, it is difficult to assess the cardiovascular risk linked to the apolipoprotein(a) gene of a subject; indeed a cut-off of apolipoprotein(a) polymorphism has not been established. The aim of this investigation was to identify an 'operative' cut-off that discriminates apolipoprotein(a) isoforms associated with high genetic risk for coronary heart disease. METHODS: Two hundred and fifty-one patients with coronary heart disease and 284 controls were recruited. Apolipoprotein(a) isoforms were detected using a high-resolution phenotyping method. RESULTS: Twenty-seven apolipoprotein(a) isoforms with apparent molecular weight varying from 280 to 820 kDa were identified. Several cut-offs of apolipoprotein(a) polymorphism were used in order to compare the frequencies of apolipoprotein(a) isoforms of low and high molecular weight between patients and controls: the cut-off between 640 and 655 kDa had the highest chi 2 (130.40). Even when possible differences in apolipoprotein(a) phenotypes (subjects with at least one isoform of low molecular weight and subjects with only isoforms of high molecular weight) were assessed, the same cut-off showed the highest chi 2 (122.47). Multivariate analysis showed that apolipoprotein (a) isoforms had the greatest predictive value for coronary heart disease (F value = 107.0720), when the cut-off between 640 and 655 kDa was used. CONCLUSIONS: The cut-off between 640 and 655 kDa appears to be the most efficient in identifying subjects at high cardiovascular risk linked to apolipoprotein(a) gene, since this cut-off discriminates apolipoprotein(a) isoforms expressing a greater risk for coronary heart disease.

Aged↗
PubMed1997

Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary heart disease in patients with essential hypertension.

BACKGROUND: Besides hypertension, several cardiovascular risk factors can play a role in the development of coronary heart disease (CHD) in hypertensive patients. Lipoprotein(a) [Lp(a)] is an important and independent cardiovascular risk factor, but its role in the development of CHD in hypertensives has not been studied. OBJECTIVE: To investigate whether or not Lp(a) levels and isoforms of apolipoprotein(a) [apo(a)] are predictors of CHD in patients with essential hypertension. METHODS: Lp(a) levels and apo(a) polymorphism were evaluated in 249 patients with essential hypertension, in 142 non-hypertensive patients with CHD and in 264 healthy controls. RESULTS: Hypertensives with CHD (n = 61) had Lp(a) levels [19 (range 0.5-73.5) versus 7 mg/dl (range 0-83.5), P < 0.001] and a percentage of apo(a) isoforms of low (< 655 kDa) relative molecular mass (RMM, 59.2 versus 25.9%, P < 0.001) higher than did those without CHD (n = 188). Moreover, there were more subjects with at least one apo(a) isoform of low RMM in the subgroup of patients with CHD than there were in that of those without CHD (80.3 versus 30.8%, P< 0.001). Lp(a) levels and apo(a) polymorphism did not differ significantly between hypertensive and non-hypertensive patients with CHD. Stepwise regression analysis indicated that high Lp(a) levels (P= 0.002073) and particularly the presence of at least one apo(a) isoform of low RMM (P < 0.000001) are strong predictors of CHD in hypertensive patients. CONCLUSIONS: Our data show that high Lp(a) levels and the presence of at least one apo(a) isoform of low RMM are strong and independent genetic risk factors for CHD in hypertensive patients. These findings suggest that Lp(a) and apo(a) isoforms should be assessed together with other cardiovascular risk factors to establish the overall CHD risk status of each hypertensive patient

Aged↗
PubMed1997

Hyperamylasemia due to macroamylasemia in adult gluten enteropathy.

We report hyperamylasemia due to macroamylasemia in a 33-year-old-woman with gluten enteropathy. Macroamylasemia was demonstrated by precipitation of 97% of amylase activity with PEG 6000. It was associated with increased serum IgA, with elevated values of specific IgA antibodies against alpha-gliadin and with a high titre of IgA anti-endomysium antibodies. Macroamylasemia disappeared after 2 months of a strict gluten-free diet. These data suggest that the increased IgA concentration in adult gluten enteropathy led to increased macroamylase formation.

Adult↗
PubMed1996

Insulin resistance shows selective metabolic and hormonal targets in the elderly.

There has been no simultaneous evaluation of different aspects of insulin action in ageing. We studied 12 elderly (77 +/- 2 years) and 12 young (26 +/- 1 years) subjects with normal glucose tolerance and matched for sex, body mass index, lean body mass (LBM), blood pressure and physical activity, using a euglycaemic-hyperinsulinaemic clamp at about 350 pmol L-1 in combination with [3H]-glucose infusion. In the elderly group, hepatic glucose production was normal, fasting serum insulin and C-peptide were significantly increased (P = 0.001) and glucose utilization (34.4 +/- 2.4 vs. 44.4 +/- 3.2 mumol kg-1 LBM min-1, P = 0.02) and the percentage maximal suppression of C-peptide (58 +/- 6% vs. 79 +/- 5%, P = 0.02) during the clamp were reduced. Fasting plasma free fatty acid (FFA) and glycerol levels were similar in the two groups, but their percentage maximal suppression during the clamp was reduced in the elderly group (FFA 45 +/- 5% vs. 77 +/- 6%, P = 0.001; glycerol 43 +/- 5% vs. 76 +/- 3%, P = 0.001). Branched-chain amino acids (valine, leucine, isoleucine) and glucagon levels were similar in the two groups, both while fasting and during the clamp. Thus, insulin resistance in ageing appears selective on glucose utilization, inhibition of lipolysis and feedback inhibition of the B-cell secretion.

Adult↗
PubMed1996

Lipoprotein(a) plasma concentrations, apolipoprotein (a) polymorphism and family history of coronary heart disease in patients with essential hypertension.

AIM: The purpose of the study was to investigate lipoprotein (a) (Lp(a)) levels and apolipoprotein (a) (apo(a)) phenotypes, and their relationship with a family history of coronary heart disease (CHD) in patients with essential hypertension (EH). METHODS: One hundred and eight newly diagnosed patients with mild to moderate EH and 159 controls were studied. Lp(a) levels were determined with an ELISA method. Apo(a) isoforms were identified by a capillary immunoblotting technique. RESULTS: Lp(a) levels and frequency distribution of apo(a) isoforms did not show significant differences between patients and controls. Lp(a) levels in hypertensives with a family history of CHD were significantly higher than in those without a family history of CHD (P < 0.01). Hypertensives with a family history of CHD showed significantly different frequencies of apo(a) isoforms to those without a family history of CHD (P < 0.05). In EH patients with a family history of CHD, apo(a) isoforms of low molecular weight (MW) had a higher prevalence (62.6%), while in hypertensives without a family history of CHD, apo(a) isoforms of high MW were prevalent (81.6%); the difference between the two subgroups was significant (P < 0.001). Multivariate analysis showed that both Lp(a) levels and apo(a) isoforms of low MW are significant variables in distinguishing between the subgroups. CONCLUSIONS: Lp(a) levels and apo(a) phenotypes do not differ between hypertensives and controls. High Lp(a) levels and apo(a) isoforms of low MW are strongly associated with a family history of CHD in hypertensives. The quantification of Lp(a) levels and the characterization of apo(a) phenotypes may be used for assessment of familial predisposition to CHD in hypertensives.

Apolipoproteins↗
PubMed1995

Early metabolic treatment after liver transplant: amino acid tolerance.

OBJECTIVE: We investigated the amino acid (AA) tolerance during Total Parenteral Nutrition (TPN) in adult patients undergone liver transplant (LTX). DESIGN: The treatment (Glucose and AA), induced on the 2nd postoperative day, was later maintained with 27 kcal/kg Ideal Body Weight (IBW) as glucose and 0.12 (12 patients: protocol #1), 0.18 (10 patients: protocol #2) and 0.25 g nitrogen (N)/kg IBW (13 patients: protocol #3) till end of the 6th postoperative day. The N intake was sequentially modified in protocol #2 and #3 to increase the supply of the amino acid (AA) that resulted in an infusion plasma level below the expected "normal" range (between 1 and 1.6 times the overnight fasting plasma level of volunteer). PATIENTS: 35 consecutive adult patients without diabetes and organ failures for the entire study period. MEASUREMENTS: Plasma AA profile was measured before LTX and at the last TPN day under continuous infusion. During #1 and #2 protocol, many AA resulted below or at the lower range of the norm while, during 0.25 gN/kg IBW infusion, the majority of the administered AA significantly increased with respect to reference values. Nevertheless, they remained in the "normal" plasma range indicating that they were supplied in an optimal amount (particularly the aromatic and sulphurated ones, potentially toxic if liver function is impaired, and the branched chain AA (BCAA) given at consistent dosage: 0.5 g/kg). Arginine resulted significantly increased (Arg: 1.9 times the reference) and cystine (Cys: 0.45), serine (Ser: 0.8) and taurine (Tau: 0.85) remained significantly lower than "normal" as well as the not administered citrulline (Cit: 0.58) and alfa amino butyric acid (Aba: 0.41). The AA (and calorie) load almost balanced the N losses during the 5th (0.411 +/- 0.038) and 6th study day (0.305 +/- 0.019 gN/kg). CONCLUSIONS: 0.25 gN/kg could be considered the minimum N load in the uncomplicated adult LTX recipients, for reassuring a balanced plasma AA pattern and body N turnover in the early postoperative phase.

Adolescent↗
PubMed1995

Kinetic of body nitrogen loss during a whole day infusion and withdrawal of glucose and insulin in injured patients.

OBJECTIVE: To investigate the kinetics of body nitrogen (N) excretion during 24 h glucose infusion (relating glycemia with insulin supply) and during subsequent 24 h saline infusion in injured patients during a full blown stress reaction. To define the lag time between the start of the withdrawal of glucose and insulin infusion, and the modification in the N loss from the body, and the time span to reach the maximum effect and its size. The knowledge of these variables is mandatory to plan short term studies in critically ill patients, while assuring the stability of the metabolic condition during the study period, and also to assess the possible weaning of the effect on protein breakdown during prolonged glucose and insulin infusion. DESIGN: 24-36 h after injury, patients were fasted ( < 100 g glucose) for 24 h (basal day). Thereafter, a 24 h glucose infusion in amount corresponding to measured fasting energy production rate (EPR), clamping glycemia at normal level with insulin supply followed by 24 h saline infusion, was performed. Total N, urea and 3-methyl-histidine (3-MH) in urine were measures on 4 h samples starting from 20th h of the basal day. SETTING: Multipurpose ICU in University Hospital. PATIENTS: 6 consecutive patients who underwent accidental and/or surgical injury, immediately admitted for respiratory assistance (FIO2 < 0.04). Excluded patients were those with abnormal nutritional status, cardiovascular compromise and organ failures. MAIN RESULTS: Patients showed a 33% increase in measured versus predicted fasting EPR and a consistent increase in N and 3-MH urinary loss. An infusion of glucose at 5.95 +/- 0.53 mg/kg x min (97.20 +/- 0.03% of the fasting measured EPR) with 1.22 +/- 0.18 mU/kg x min insulin infusion reduced N and 3-MH loss after a time lag of 12 h. The peak decrease in body N (-36%) and 3-MH loss (-38%) was reached during the first 12 h of glucose withdrawal period. Thereafter, during the following 12 h, the effect completely vanished confirming that it is therapy-dependent and that the metabolic environment of the patients did not change during the three days study period. CONCLUSION: 24 h glucose withdrawal reduces N and 3-MH loss injured patients, the drug-like effect is maintained during the first 12 h of withdrawal and thereafter disappears. The study suggests that at least a 24 h study period is necessary when planning studies exploring energy-protein metabolism relationship in injured patients, and, again 24 h before changing protocol in a crossover study.

Adolescent↗
PubMed1995

Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio.

An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p < 0.01) and decreased after drug discontinuation in both groups. Nitric oxide levels were significantly related with those of the effective renal plasma flow (p < 0.02), but not with the glomerular filtration rate. Proteinuria levels significantly decreased after drug administration (p < 0.009) in group 1 and returned to baseline levels thereafter, except two cases showing persisting low levels. Values of filtration fraction in the same group decreased after iso5M administration (p < 0.02 compared to basal levels). These results may possibly be related to the counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.

Adult↗
PubMed1993

Characterization of apo(a) polymorphism by a modified immunoblotting technique in an Italian population sample.

Apo(a), the specific lipoprotein(a) (Lp(a)) apolipoprotein, is characterized by different isoforms (from 6 to 11 on SDS-PAGE) encoded by a system of autosomal codominant alleles. Electrophoresis on agarose gel displays a better resolving power than SDS-PAGE (a larger number of apo(a) isoforms is detected). The aim of this work was to set up a simple technique that uses a capillary blotting apparatus and a polyvinylidene difluoride membrane for protein transfer. We tested an Italian population sample of 202 healthy subjects (123 men and 79 women) and we detected 22 apo(a) isoforms varying from 280 to 775 kDa. In our sample, 135 subjects (66.5%) had a single-band phenotype, 64 (31.7%) had a double-band phenotype and 3 subjects (1.5%) had no detectable bands ('null' phenotype). This simple and reproducible technique could be applied in the genetic screening of apo(a) polymorphisms and for clinical investigations of the risk of developing cardiovascular diseases.

Adult↗
PubMed1993

Cancer cachexia, malnutrition, and tissue protein turnover in experimental animals.

The role of malnutrition in the development of cachexia in rats bearing the Yoshida ascites hepatoma AH-130 was investigated by comparing the changes in tissue protein turnover in these animals with those observed in pair-fed controls. The tumor elicited in rats an early and conspicuous loss of body weight and tissue waste. Protein loss was particularly prominent for the gastrocnemius muscle and the heart and less pronounced for the soleus, while the diaphragm was little affected. Liver, kidneys, and spleen transiently increased in weight then regressed and eventually atrophied, while adrenals were enlarged over the whole experimental period. Protein waste was mainly due to acceleration of tissue protein breakdown, this protein hypercatabolic state being associated with increased cathepsin D activity in liver and gastrocnemius. In pair-fed animals the liver showed a marked protein loss resulting from enhanced catabolism, while the sharp decrease of heart protein content and the less prominent waste of the gastrocnemius were due to a reduction in protein synthesis. The total plasmatic concentration of free amino acids in AH-130-bearing rats was decreased at Day 4, when the tumor was actively proliferating, and returned to control values at Day 10, when the tumor had reached a stationary state. On the contrary, in pair-fed animals total plasma amino acids decreased over the whole experimental period. Plasma branched-chain amino acids were unchanged or even decreased in tumor hosts, while the Gly/Pro ratio was elevated in pair-fed rats. The intracellular concentration of free amino acids was higher in stationary than in exponentially- growing tumors, reflecting the enhanced proteolytic rates observed in stationary tumor cells. On the whole, the results suggest that reduced food uptake and metabolic competition by the tumor are not sufficient to justify the marked hypercatabolism in host tissues during the AH-130 hepatoma growth. The profound differences between tumor-bearing and pair-fed animals suggest that, if malnutrition undoubtedly played a role in this model of cancer cachexia, its effects were overwhelmed and subverted in the frame of the tumor-host interplay that dictated a distinctively peculiar syndrome.

Amino Acids↗
PubMed1992

[Optimal dose of amino acids administered in total parenteral nutrition (TPN) of malnourished patients].

A plasmatic concentration for each aminoacid, between 1 and 1.5 times the normal value in fasting healthy subjects, is considered as an optimal target during total parenteral nutrition (TPN) in malnourished patients. We have analyzed the correlation between the aminoacid input and the aminoacid plasmatic concentration during TPN at different aminoacid composition. By exponential regression curves we then calculated the input required to keep each aminoacid plasma concentration in the optimal range.

Amino Acids↗