Biomedical subjects

G Mingrone

Publications and source records attributed to G Mingrone.

At least 91 records · Page 5Linked to original sources

PubMed1996

Increased resting lipid oxidation in Crohn's disease.

Resting energy expenditure (REE) was measured by indirect calorimetry and body composition was assessed by both direct (bioimpedance) and indirect (anthropometry) methods in 20 hospitalized patients with biopsy-proven ileal Crohn's disease and in a group of 16 healthy volunteers matched for sex, age, and height with the patient group. The Crohn's disease activity index was below 120 in all patients studied, who were treated with a low dose of corticosteroids (0.2-0.3 mg/kg body wt of prednisone). The average weight of Crohn's patients was significantly lower than that of controls (55.70 vs 70.50 kg, P < 0.001) due to both lower fat mass (9.97 vs 18.30 kg, P < 0.001) and lower lean body mass (45.72 vs 52.20 kg, P < 0.02). The average REE was significantly higher in the control group (1785.42 +/- 7.503 vs 1559.1 +/- 48.39 kcal/day, P < 0.001). However, these differences disappeared when REE was normalized by lean body mass (LBM) (34.49 +/- 2.56 vs 34.704 +/- 3.75 kcal/kg LBM P = NS). The nonprotein respiratory quotient was significantly lower in the patient group (0.823 +/- 0.031 vs 0.882 +/- 0.012, P < 0.025), indicating an increased lipid oxidation. This increased lipid oxidation might explain the reduced fat stores found in the group of Crohn's patients, suggesting also that a sufficiently lipid-rich diet could be useful in their nutritional management.

Adult↗

PubMed1996

Twenty-four-hour energy and nutrient balance in weight stable postobese patients after biliopancreatic diversion.

To better understand the long-term weight stability of postobese patients who underwent biliopancreatic diversion (BPD), we studied 24-h energy and nutrient balance in eight women at least 3 yr after surgery (PO) and compared the results to those obtained in eight normal never-obese control women (C), matched by age and weight. Body composition was measured by dual-energy x-ray absorptiometry (DXA). All the patients were on an ad libitum diet; 24-h energy and nutrient intake were measured on the experimental day. Twenty-four-hour energy expenditure (EE) and 24-h nutrient oxidation rates were measured in a respiratory chamber, and energy and nutrient balances were calculated after correcting for 24-h fecal nutrient loss. No differences in body composition were found between PO and C. PO had a higher gross energy intake than C (10.6 +/- 3.4 vs. 8.0 +/- 2.2 MJ/d; p < 0.05); however, due to the higher energy fecal loss in PO as compared to C (2.4 +/- 1.3 vs. 0.09 +/- 0.01 MJ/day; p < 0.01), 24-h metabolizable energy intake (MEJ) was not different in the two groups. The energy fecal loss in the PO patients was mostly in the form of lipid. EE at 24 h was not different in PO as compared to C. Therefore energy balance, computed as the difference between 24-h MEI and 24-h EE, was similar in the two groups. Respiratory quotient was significantly higher in PO than in C (1.00 +/- 0.08 vs. 0.83 +/- 0.03; p < 0.01). Carbohydrate (-135 +/- 37 g/d in PO vs. 63 +/- 23 g/d in C; p < 0.001), and lipid (48 +/- 14 g/d in PO vs. -23 +/- 6 g/d in C; p < 0.001) balances were different in the two groups. We conclude that chronic lipid malabsorption was the main metabolic abnormality explaining the achievement of energy balance in postobese subjects after biliopancreatic diversion. A chronic reduction of lipid absorption seems to play a key role in the long-term weight stability of this group of postobese subjects.

Adult↗

PubMed1996

NONMEM improves group parameter estimation for the minimal model of glucose kinetics.

The minimal model of glucose kinetics interprets blood glucose and insulin concentrations after an interprets blood glucose and insulin concentrations after an intravenous glucose tolerance test (IVGTT) and provides parameters describing tissue insulin sensitivity and glucose-dependent tissue glucose disposal. In the standard application, the model is fitted to each experimental subject's points by nonlinear least squares, with suitable weighing. The variability of parameter estimates may, however, represent a problem, making the model in practice unidentifiable on a group of experimental subjects undergoing some treatment of interest. To obviate this problem, a specific modification to the original protocol has been introduced: administering tolbutamide 20 min after the glucose bolus has been shown to improve parameter stability. With this modification, however, the converse model of pancreatic secretion can no more be fitted on the collected series of concentrations. The application of the nonlinear mixed effects model (NONMEM) loss function allows estimation of parameter population means, variances, and covariances to be made on all sampled subjects simultaneously. Although this procedure does not allow an individual subject's parameters to be estimated, the variability of the group parameter estimates is greatly reduced compared with the standard method. In the present work, 20 healthy volunteers have been studied with an IVGTT, and group parameters have been computed in both standard and NONMEM ways: asymptotic parameter coefficients of variation with NONMEM were at least twenty times smaller than the corresponding sample parameter coefficients of variation obtained with the classical method.

Adult↗

PubMed1995

An improved GLC method for a rapid, simultaneous analysis of both medium chain fatty acids and medium chain triglycerides in plasma.

An improved gas-liquid chromatographic (GLC) method for the direct, simultaneous analysis of both medium chain monocarboxylic acids (MCFA) and medium chain triglycerides (MCT) is reported. The calibration curve of MCFA and MCT is linear in the range from 30 ng to 1000 ng. Five nanograms for tricaproin (MCT-6), 10 ng for tricaprylin (MCT-8) and 15 ng for tricaprin (MCT-9) represent the GLC detection limits of MCT, while those of MCFA range from 40 to 15 ng depending on their chain length: the longer the chain length, the higher the detection limit. The recovery of MCFA range from 79 to 99% and that of MCT from 85 to 99%. An example of plasma concentration curves of MCT and MCFA after an intravenous bolus injection of an MCT emulsion (100 mg MCT/kgbw) in a patient with Crohn's disease is shown.

Adult↗

PubMed1995

Free fatty acid analysis in ascitic fluid improves diagnosis in malignant abdominal tumors.

The fasting concentration of free fatty acids (FFA) in the ascitic fluid was determined in 14 patients with malignant ascites and in 19 patients with liver cirrhosis. In malignant ascites FFA levels were increased more than three times when compared with the levels in cirrhotic ascites (5.241 +/- 0.493 vs. 1.558 +/- 0.170 mumol/ml; P < 0.0001). Palmitic acid was the most representative saturated FFA (which together accounted for 2.499 +/- 0.323 vs. 0.833 +/- 0.064 mumol/ml; P < 0.0001), while unsaturated FFA (2.741 +/- 0.298 vs. 0.725 +/- 0.111 mumol/ml; P < 0.001) were represented, in decreasing order, by oleic, linoleic and arachidonic acids. The ratio of unsaturated to saturated FFA was higher in neoplastic patients (1.35 +/- 0.29 vs. 0.826 +/- 0.065 P < 0.05). Albumin concentration in ascitic fluid of neoplastic patients was 22.44 +/- 1.35 g/l, while that of cirrhotic patients was 8.19 +/- 0.32 g/l, P < 0.0001. A close relationship (R2 = 95.14%) between albumin concentration in ascitic fluid and levels of total FFA was found. These data support the hypothesis that the elevation of FFA in ascitic fluid allows discrimination between malignant and non-malignant ascites.

Adult↗

PubMed1995

Effects of dexfenfluramine on free fatty acid turnover and oxidation in obese patients with type 2 diabetes mellitus.

To test the potential effects of dexfenfluramine (dF) on enhancing free fatty acid (FFA) turnover and oxidation rates, 11 obese female non-insulin-dependent diabetes mellitus (NIDDM) outpatients (age, 52.5 +/- 1.5 years; weight, 81.3 +/- 3.2 kg; height, 158 +/- 3.04 cm; body mass index, 32.4 +/- 0.7 kg/m2) received a primed-constant infusion of 1-14C-palmitate. The waist to hip ratio (WHR) was 0.91 +/- 0.04. Fat body mass and lean body mass, assessed by dual-energy x-ray densitometry, were 32.0 +/- 1.5 and 49.30 +/- 2.67 kg, respectively. All patients had an average hemoglobin A1 of 6.3% +/- 0.3% in the month preceding the study and had not received oral hypoglycemic agents. Gas exchange was measured both basally and during a ventilated-hood system, indirect-calorimetry session. The protocol was a randomized, placebo-controlled, single-blind design. Subjects received dF 30 mg acutely (n = 6) or a placebo (n = 5). A dose of dF 15 mg twice daily or placebo was then administered over 15 days (chronic). To obtain serum peak level of the drug, dF was administered 2 hours before starting palmitate infusion. A free diet was allowed throughout the study, and the group treated with dF lost approximately 0.5 kg body weight. Acute and chronic dF administration resulted in a significant increase in FFA oxidation, expressed as a percentage of the dose of radiocarbon (respectively, 11.47% +/- 0.46% v 9.50% +/- 0.46% [P < .01] and 12.06% +/- 0.71% v 9.88% +/- 0.62% [P < .01]). FFA turnover rate was higher after both acute and chronic dF administration (respectively, 10.71 +/- 2.18 v 7.79 +/- 1.48 mumol/kg/min [P < .05] and 11.92 +/- 2.74 v 8.43 +/- 1.86 mumol/kg/min [P < .05]). Serum FFA concentration during both acute and chronic dF administration increased, but not significantly. Mean serum glucose level decreased after acute dF from 114.3 +/- 8.6 to 86.5 +/- 5.1 mg/dL (P < .001) and after chronic dF from 120.3 +/- 7.3 to 89.8 +/- 5.8 mg/dL (P < .001). Serum insulin was not affected by dF administration. In conclusion, oral acute and chronic dF administration increase FFA turnover and oxidation rates in NIDDM obese patients. This may play an important role in weight reduction. In addition, dF shows a weight-independent effect on glucose metabolism, reducing serum glucose levels without acting on insulin secretion.

Diabetes Mellitus, Type 2↗

PubMed1995

Dicarboxylic acids, an alternate fuel substrate in parenteral nutrition: an update.

Dicarboxylic acids (DA) are formed from the omega-oxidation of monocarboxylic acids when the beta-oxidation of free fatty acids is impaired. Medium-chain DA have the peculiar characteristic of being water soluble due to the presence of two carboxylic terminal groups in the molecule. Contrary to both long- and medium-chain triglycerides which are administered as emulsions, they can be given by a peripheral vein as inorganic salts. DA are beta-oxidized at level of both peroxisomes and mitochondria via carnitine-independent pathway. The products of beta-oxidation of odd-chain DA are acetyl-CoA and malonyl-CoA, which cannot be oxidized further, are used in lipogenesis. Moreover even-chain DA produce acetyl-CoA and succinyl-CoA, which is a gluconeogenetic precursor. Azelaic acid (C9), does not show acute or chronic toxicity effects in animals but much of it is lost in urine (more than 50% of the given dose). Sebacic acid (C10) is lost in urine to a smaller extent (about 12% of the administered dose) and its energy density (6.64 kcal/g) is greater than that of C9 (4.97 kcal/g). Dodecanedioic acid (C12) seems to be the best candidate for parenteral nutrition, because it is eliminated in the urine only in minimal amounts (3.90% of the given dose), it is rapidly utilized by tissues, and it has a high energy density (7.20 kcal/g).

Journal Article↗

PubMed1995

Daily energy metabolism in patients with type 1 diabetes mellitus.

OBJECTIVE: We evaluated the daily energy balance and main substrate utilization in Type 1 insulin dependent diabetic patients and healthy volunteers. METHODS: Ten patients with Type 1 diabetes mellitus and eight healthy volunteers were studied. Diabetic patients were well controlled under intensive insulin treatment (0.6 UI/kg body weight, HbA1c = 5.5 +/- 0.7%). During the 30 hours each subject spent in the respiration chamber VO2, VCO2, respiratory quotient, daily energy intake, 24-hour, day-time, night-time and basal energy expenditure as well as energy expenditure during exercise (at 40% maximal exercise capacity), main substrate oxidation (carbohydrates, lipids and proteins) and overall diet-induced thermogenesis, were measured. The results were corrected for 24-hour urinary nitrogen loss. RESULTS: Diet-induced thermogenesis, expressed as percent of energy intake, was found to be significantly lower in diabetic patients than in control subjects (6.69 +/- 1.29% vs 11.8 +/- 4.71% of energy intake, p < 0.05). A negative correlation was found between diet-induced thermogenesis and daily average glycemia for diabetic patients (r = -0.65, p < 0.01). Energy expenditure during exercise, calculated in terms of net work efficiency, was not different between the two groups. CONCLUSIONS: In conclusion, since diet-induced thermogenesis is highly correlated with the theoretical cost of glucose storage and since no difference was found in carbohydrate oxidation, glucose storage in diabetic patients is probably reduced when hyperglycemia occurs. Diabetic patients in good metabolic control are able to perform mild exercise with a work efficiency very similar to that of control subjects.

Adult↗

PubMed1995

Biliary aminopeptidase-N and the cholesterol crystallisation defect in cholelithiasis.

Several biliary proteins have cholesterol crystallisation promoting activity. One of these glycoproteins is aminopeptidase-N, a canalicular ectoenzyme. This study attempted to localise aminopeptidase-N along the biliary tree, to assess its concentration in a series of 98 patients subjected to abdominal surgery, 40 of them without gall stones, and to correlate its concentration with cholesterol crystal formation time of gall bladder bile. Aminopeptidase-N was isolated from purified native biliary vesicles. A specific polyclonal rabbit anti-aminopeptidase-N antibody was prepared for quantitative immunoblotting and for immunolocalisation. Tissue was obtained from liver biopsy specimens and from gall bladders removed at surgery because of gall stone disease. Aminopeptidase-N was immunolocalised to the apical membranes of hepatocytes and to the apical pole of ductular and gall bladder mucosal cells. The nucleation time of gall bladder bile was mean (SD) 4 (3) days in the gall stone group, compared with 21 (18) days in the control group (p < 0.001). Total absolute biliary protein and aminopeptidase-N concentrations were similar in both the control and gall stone patients. There was a reciprocal significant correlation, however, between the nucleation time and the relative aminopeptidase-N concentration (r = -0.35, p < 0.01) only in the gall stone group of patients. This study shows that this apical transmembrane ectoenzyme with cholesterol crystallisation promoting activity is present along the biliary tree and the hepatocyte. These findings support the concept that high concentrations or qualitative changes of biliary aminopeptidase-N contribute to cholesterol gall stone formation.

Adult↗

PubMed1994

PC-based differential model fitting as a support for clinical research.

A PC-based minimisation software written in C-language is described, which solves numerically both simple non-linear regression problems and problems expressed as systems of (unsolved) initial-value ordinary or partial differential equations. The software uses second-order iterated Runge-Kutta algorithm to approximate numerically the solution curves. It uses a quasi-Newton algorithm to minimize either sums of squares (weighted or unweighted) or NONMEM loss functions. Inverse Hessian approximation to the parameter dispersion and Monte Carlo generation of artificial samples are offered to test the robustness of the parameter values obtained. A real test problem is described, involving the hydrolysation of plasma Medium Chain Triglycerides to Free Fatty Acids and the uptake of these from plasma. Two competing models were evaluated, one involving linear terms for each transfer and one involving carrier-mediated, rate-limited hydrolysis and tissue absorption steps. The simpler linear model was found to be more robust and eventually used to describe the experimental data.

Algorithms↗

PubMed1994

Protective role of biliary cholesterol and phospholipid lamellae against bile acid-induced cell damage.

BACKGROUND/AIMS: Bile salts (BS) are cytotoxic agents, but cell damage is not observed in the hepatobiliary system. We hypothesized that biliary lipid vesicles (unilamellae and multilamellae) could have a protective role against BS-induced cytotoxicity. METHODS: Biliary lipid lamellar secretion was induced by feeding rats with 0.5% diosgenin. Cytoprotection was assessed in bile duct-obstructed rats and by incubating human erythrocytes with sodium taurocholate. RESULTS: Biliary cholesterol concentration increased > 300% in diosgenin-fed rats; electron microscopic examination showed a great abundance of lipid lamellar vesicles in bile and within the canaliculi. After bile duct obstruction, serum hepatic enzyme activities were significantly lower in diosgenin-fed rats. Histologically severe and confluent hepatocellular necrosis was only observed in control rats. Biliary lamellar lipid material significantly reduced the BS-induced hemolytic effect in vitro in a concentration-dependent manner. This protective effect correlated to a progressive decrease in the intermicellar BS concentration. Phosphatidylcholine or cholesterol, alone or as lamellar structures, also showed cytoprotective effect in vitro but always less than native biliary lamellae. CONCLUSIONS: These results support the concept that native biliary cholesterol phospholipid lamellae represent an important cytoprotective factor for hepatocytes and biliary epithelial cells against BS-induced damage.

Animals↗

PubMed1994

Glucose-induced thermogenesis in postobese women who have undergone biliopancreatic diversion.

We evaluated the metabolic response to a standard (75-g) oral-glucose-tolerance test (OGTT) in eight post-obese women (PO) who underwent biliopancreatic diversion and in eight healthy control women (C). All subjects had been weight-stable for > or = 2 y. Blood samples for glucose, insulin, C-peptide, and nonesterified free fatty acids were taken at baseline and during 180 min after the glucose load. Plasma glucose and insulin concentrations at baseline and during the OGTT were similar in the two groups, suggesting the absence of an insulin-resistant state in the PO. Continuous indirect calorimetry was performed throughout the test. Glucose-induced thermogenesis (GIT) was higher in PO than in C (8.6 +/- 2.6 vs 4.3 +/- 1.9%; P < 0.01). These data indicate that GIT and insulin-glucose metabolism are not impaired in postobese patients when a near ideal body weight is reached and maintained after weight loss; this suggests that thermogenic deficiencies and hyperinsulinemia-insulin resistance are alterations secondary to obesity.

Adult↗

PubMed1994

Normalization of Insulin Sensitivity in the Obese Patient after Stable Weight Reduction with Biliopancreatic Diversion.

Insulin resistance is a common feature in obese patients. To evaluate the modifications in insulin sensitivity after a bariatric operation such as Bilio-pancreatic diversion (BPD), three groups of subjects (14 normal controls (N); seven ex-obese patients (X) with at least 2 years at weight-stable conditions after BPD surgery; and eight morbidly obese patients (0)) were studied with intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The ratio of the area under the curve (AUC) for glucose over that of insulin was used as a measure of insulin sensitivity. All the following tests were conducted as Bonferroni-corrected pairwise t-tests, in case overall ANOVA was significant. No significant difference was found between N and X subjects, while obese patients showed a reduced AUCg/AUCI ratio with respect to the normal controls (O vs N: 0.01164 +/- 0.00039 vs 0.02392 +/- 0.0039, p < 0.05). IVGTT, AUCS: significant differences were found in each case: N vs X: 0.0591 +/- 0.0075 vs 0.1402 +/- 0.0399, p < 0.05; N vs 0:0.0591 +/- 0.0075 vs 0.0223 +/- 0.0031, p < 0.01; X vs 0:0.1402 +/- 0.0399 vs 0.0223 +/- 0.0031, p < 0.05. IVGTT-derived data were also analyzed using the minimal model of glucose kinetics; with this method, glucose effectiveness was significantly different between normal subject and obese subjects (0.0248 +/- 0.00288 Vs 0.00906 +/- 0.00135 per min, p < 0.001). The insulin sensitivity index was not significantly different between normal and ex-obese subjects, while both of these groups were significantly different from obese patients (N vs 0: 12.04 x 10&sup5; +/- 2.61 x 10&sup5; vs 3.29 x 10&sup5; +/- 0.61 x 10&sup5;, p < 0.066; X vs 0: 16.42 x 10&sup5; +/- 4.23 x 10&sup5; vs 3.29 x 10(1)+/- 0.61 x 10&sup5; per min per pM, p < 0.02). In conclusion, the present study indicates that, after a body weight reduction operation capable of almost re-establishing ideal body weight like BPD, obese individuals with a family history of obesity show a normalization of insulin response to glucose load.

Journal Article↗

PubMed1994

[Artificial nutrition in the injured patient].

Current knowledge of physiopathology allows better understanding of the metabolic and immunological alterations that occur after trauma, thus allowing more adequate treatment. Nutritional support is recognized as an important therapeutic intervention to promote wound healing, reduce the risk of infection and improve survival. The patient with severe trauma needs nutritional support from the beginning of treatment. The early administration of enteral nutrition is an important factor in the reduction of gut bacterial translocation and thus of septic complications. In the early phase, the parenteral route is capable of providing a sufficient calorific and protein support, whilst awaiting the recovery of the enteral route.

Humans↗

PubMed1993

Serum bile acid concentrations in mild liver cirrhosis.

Fasting serum conjugated bile salt concentrations were measured in a group of 20 patients with moderate post-hepatitis cirrhosis. Twenty healthy volunteers were used as controls. The individual conjugated bile acids were analyzed by a specific and sensitive method which couples reversed-phase high-performance liquid chromatography with mass spectrometry. Significantly elevated levels of the total and individual conjugated bile acids were found in cirrhotic patients. The predominant serum bile acids were conjugates of chenodeoxycholic acid. The conjugates of lithocholic acid were also increased; in subjects with normal liver function, on the contrary, they were found only in traces.

Adult↗

PubMed1993

Cholesterol crystallization-promoting activity of aminopeptidase-N isolated from the vesicular carrier of biliary lipids.

Different hydrophobic glycoproteins are associated to native biliary vesicles, which are the major carrier of biliary cholesterol. Some of these proteins promote cholesterol crystallization, a key step in cholesterol gallstone formation. This study was specifically conducted to identify the 130 kDa biliary vesicle-associated glycoprotein and to determine its in vitro effect on the cholesterol crystal formation time. The 130 kDa vesicular glycoprotein was identified as aminopeptidase-N by amino acid sequencing and specific enzymatic assay. Polyclonal antibodies raised against aminopeptidase-N allowed us to determine its concentration in human hepatic bile, which varied from 17.3 to 57.6 micrograms/ml. Aminopeptidase-N showed a concentration-dependent cholesterol crystallization activity when it was added to supersaturated model bile at a concentration range usually found in native bile. Because of this promoting effect on in vitro cholesterol crystal formation, we suggest that biliary aminopeptidase-N may play a critical role in the pathogenesis of cholesterol gallstone disease.

Amino Acid Sequence↗

PubMed1993

Sebacic acid binding to human plasma albumin.

Sebacic (decanedioic) acid is a dicarboxylic acid proposed recently as an alternative energy substrate in total parenteral nutrition. In this paper, binding of sebacic acid to defatted human plasma albumin, also in the presence of decanoic acid, was studied by means of equilibrium dialysis. In addition, the binding of sebacic acid in human serum was investigated. Binding to defatted albumin was analysed by a model with two independent classes of sites with different affinity constants. The fitting procedure took into account some of the measurement errors that are likely to affect the equilibrium dialysis technique. We found for sebacic acid one binding site with affinity constant 3.69 x 10(4) M-1 and four to five sites with affinity constant 7.14 x 10(2) M-1. Association constants for decanoic acid are 3-4-fold larger than those of sebacic acid. Data of binding of sebacic acid in human serum suggested that only three to five of the low affinity sites are available for binding. When disodium sebacate is administered i.v. for total parenteral nutrition, a substantial fraction of sebacic anions is likely to be bound in serum.

Binding Sites↗

PubMed1993

A rapid GLC method for the direct analysis of plasma medium chain fatty acids.

A new, rapid, gas-liquid-chromatographic (GLC) method for the direct determination of plasma medium-chain fatty acids (MCFA) (from C8 to C12) which does not require derivatization procedures is described. Analysis of underivatized MCFA by GLC showed a detection limit ranging from 0.50 to 0.217 microgram depending on chain length: the longer the chain, the higher the detection limit. Compared with the HPLC and GLC methods currently described in the literature, this GLC procedure appears to be easy, adequately sensitive, accurate and well reproducible for those MCFA, like n-octanoic and n-decanoic acids, present in plasma after p.o. or i.v. MCT administration and it requires a short time (about 30 min) for complete processing.

Adult↗