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Biomedical subjects

A V Greco

Publications and source records attributed to A V Greco.

At least 73 records · Page 4Linked to original sources
PubMed1998

Cholestatic hepatitis due to ticlopidine: clinical and histological recovery after drug withdrawal. Case report and review of the literature.

A 72-year-old housewife presented with clinical and laboratory signs of acute cholestatic hepatitis. Symptoms had appeared 6 months after she was started on ticlopidine 250 mg/day. Infectious aetiologies were excluded by serology and there was no history of alcohol abuse or use of other drugs. Clinical findings were confirmed by liver biopsy. The drug was discontinued and symptoms gradually subsided. A second biopsy obtained during this phase documented complete resolution of the hepatic damage. A review of the literature shows that the late onset of hepatic toxicity in this case is unique and this is the first report to include histological documentation during the acute phase and after recovery.

Aged↗
PubMed1997

Binding of indole-3-acetic acid to human serum albumin and competition with L-tryptophan.

Indole-3-acetic acid (IAA) is a product of tryptophan (Trp) metabolism and is found to be markedly increased in uremic sera. IAA binding to defatted human serum albumin at 37 degrees C and pH 5, 7.4, and 8.5 was studied by equilibrium dialysis, and data were analyzed assuming two independent high affinity binding sites plus a class of low affinity sites. The estimated values of the association constant of dominant site were: 7.96 x 10(3) M-1 at pH 5, 11.57 x 10(3) M-1 at pH 7.4, and 6.30 x 10(3) M-1 at pH 8.5. The competition between IAA and Trp for albumin binding at pH 7.4 was investigated. The results suggest that one specific albumin site is common for IAA and Trp, but the data were not adequately predicted by a purely competitive scheme. A better prediction was achieved assuming that the binding of IAA to a site different from the common site inhibits Trp binding.

Binding Sites↗
PubMed1997

Serum uremic toxins from patients with chronic renal failure displace the binding of L-tryptophan to human serum albumin.

The level of free tryptophan (Trp) and its metabolites in serum appears to be related to some pathologic states, such as chronic renal failure and neuropsychiatric disorders, so that a precise characterization of tryptophan binding to serum albumin is of interest. In the present paper, the binding of L-tryptophan to defatted human serum albumin at 37 degrees C and at pH 7.4 was studied by means of equilibrium dialysis. The competition between L-tryptophan and serum solutes extracted from uremic patients undergoing hemodialysis, before dialysis treatment, was also investigated. Solutes were extracted from uremic pools of sera using two different deproteinization methods: serum ultrafiltration and heat denaturation of serum proteins followed by ultrafiltration. We found 1.10 +/- 0.03 binding sites for Trp to defatted albumin with an association constant 11.37 +/- 1.03 x 10(3) M-1. The competition experiments suggested that the number of Trp binding sites were not significantly modified by the addition of solutes obtained with the method of ultrafiltration with respect to the binding of L-tryptophan to albumin in the absence of competitors, while their affinity constant was markedly reduced (2.66 +/- 0.18 x 10(3) M-1). Moreover, a significant reduction of the affinity constant was observed when competitors for Trp were obtained using heat deproteinization associated with ultrafiltration (1.91 +/- 0.15 x 10(3) M-1 vs. 2.66 +/- 0.18 x 10(3) M-1; P < 0.005). These results might be ascribed to the fact that the last procedure has a higher yield with a more complete liberation of uremic toxins from serum proteins, so that they became probably totally free thus competing at higher extent with L-tryptophan for albumin binding sites.

Binding Sites↗
PubMed1997

Uptake of dodecanedioic acid by isolated rat liver.

The uptake of dodecanedioic acid (C12); a dicarboxylic acid with 12 carbon atoms, was studied in the isolated perfused rat liver. Fifty mumol of C12 were injected as a bolus into the perfusing liver solution. The concentration of C12 in perfusate samples taken over 2 h from the beginning of the experiments were analyzed by high performance liquid chromatography. An in vitro experimental session was performed to determine the binding curve of C12 to defatted bovine serum albumin. These data were then used to compute the perfusate C12 free fraction. The number of binding sites on the albumin molecule was equal to 4.29 +/- 0.21 (S.E.), while the affinity constant was 6.33 +/- 0.87 x 10(3). M-1. Experimental values of perfusate C12 concentration versus time were individually plotted and fitted to a monoexponential decay for each liver perfused. The predicted C12 concentration at time zero averaged 0.354 +/- 0.0375 mumol/ml. Prom this value the apparent volume of distribution of C12 was obtained and corresponded to 153.02 +/- 14.56 ml. The disappearance rate constant from the perfusate was 0.0278 +/- 0.0030 min-1. The C12 half life was 26.6 +/- 2.3 min. The mean hepatic clearance from the perfusate was 4.08 +/- 0.38 ml/min. In conclusion, C12 is quickly taken up by the liver so that in about 100 min it was completely cleared from the perfusate.

Animals↗
PubMed1997

Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids.

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery POI; and after reaching stable body weight, at least 2 years after surgery POII. A group of 7 control subjects (C), matched groupwise for sex, age and BMI with POII patients, was also studied. The M value at POI was significantly higher than at Ob (49.12 +/- 8.57 vs 18.14 +/- 8.57 mumol.kg-1.min-1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 +/- 7.23 vs 9.42 +/- 3.91 mumol.kg-1.min-1) and was not significantly different between POII and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/- 77.6 mumol.1(-1). The same applied to basal plasma triglycerides (2.07 +/- 0.77 vs 1.36 +/- 0.49 vs 0.80 +/- 0.19 g.1(-1). Weight decreased mainly in the late postoperative period (POI to POII 124.28 +/- 11.22 to 69.71 +/- 11.78, 83% of total decrement), rather than in the early postoperative period (Ob to POI 135.25 +/- 14.99 to 124.28 +/- 11.22 kg, 17% of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance.

Adult↗
PubMed1997

Kinetics of dodecanedioic acid and effect of its administration on glucose kinetics in rats.

Dodecanedioic acid (C12), a saturated aliphatic dicarboxylic acid with twelve C atoms, was given as an intraperitoneal bolus to male Wistar rats, with the aim of evaluating C12 suitability as an energy substrate for parenteral nutrition. The 24 h urinary excretion of C12 was 3.9% of the administered dose. C12 kinetics were investigated by a one-compartment model with saturable tissue uptake and reversible binding to plasma albumin. The analysis of plasma concentration and urinary excretion data from different animals yielded the population means of the kinetic parameters: renal clearance was 0.72 ml/min per kg body weight (BW) (much smaller than inulin clearance in the rat), and maximal tissue uptake was 17.8 mumol/min per kg BW corresponding to 123.7 J/min per kg BW. These results encourage the consideration of C12 as a possible substrate for parenteral nutrition. To investigate the effect of C12 administration on glucose kinetics, two other groups of rats, one treated with an intraperitoneal bolus of C12 and the other with saline, were subsequently given an intravenous injection of D[-U-14C]glucose in a tracer amount. Radioactivity data of both control and C12-treated rats were analysed by means of a two-compartment kinetic model which takes into account glucose recycling. The estimates of glucose pool size (2.3 mmol/kg BW) and total-body rate of disappearance (82.1 mumol/min per kg BW) in control rats agreed with published values. In C12-treated rats, the rate of disappearance appeared to be reduced to 36.7 mumol/min per kg BW and the extent of recycling appeared to be negligible.

Animal Nutritional Physiological Phenomena↗
PubMed1997

Dodecanedioic acid infusion induces a sparing effect on whole-body glucose uptake, mainly in non-insulin-dependent diabetes mellitus.

Even-numbered dicarboxylic acids (DA) have been proposed as an alternative fuel substrate in parenteral nutrition. In particular, dodecanedioic acid (C12) shows a rapid plasma clearance from tissues, a very low urinary excretion compared with other DA and a high oxidation rate. The aim of the present study was to investigate the effect of C12 infusion on insulin-stimulated glucose uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM) compared with healthy volunteers. A primed-constant infusion of C12 (0.39 mmol/min) was administered over 240 min, and at 120 min a 2 h euglycaemic hyperinsulinaemic clamp was performed. Blood specimens were sampled every 30 min and fractioned urines were collected over 24 h. The levels of C12 were measured by HPLC. Indirect calorimetry was performed continuously during the entire session. Body composition was assessed in all subjects studied to obtain fat-free mass (FFM) values. Whole-body glucose uptake decreased significantly during C12 infusion in both groups, although this effect was much more evident (P < 0.01) in NIDDM patients (52.4 (SD 15.8) % decrease compared with saline) than in controls (25.9 (SD 12.1) % decrease). The M value (mumol/kgFFM per min) was reduced by C12 to lower levels in NIDDM patients than in normal controls (12.6 (SD 3.9) v. 25.9 (SD 4.5), P < 0.01). Urinary excretion of C12 over 24 h was significantly lower in NIDDM patients than in controls (4.26 (SD 0.30) mmol v. 5.43 (SD 0.48), P < 0.01), corresponding to less than 3% of the administered dose. The infusion of C12 decreased non-protein RQ significantly in both groups of patients. In conclusion, this study shows, for the first time, that C12 significantly reduces glucose uptake in both normal controls and NIDDM patients, although this sparing effect on glucose uptake is much more pronounced in diabetic patients. These data suggest that C12 decreases glucose uptake and oxidation, mainly through a mechanism of substrate competition. Thus, it might be a useful alternative substrate in enteral or parenteral nutrition, sparing glucose utilization and increasing glycogen stores, in those clinical conditions, like NIDDM, where reduced insulin-induced glucose uptake and oxidation are observed.

Blood Glucose↗
PubMed1997

Cochlear dysfunction in IDDM patients with subclinical peripheral neuropathy.

OBJECTIVE: To investigate the function of the auditory pathway from the cochlea to the auditory cortex in subjects with IDDM. RESEARCH DESIGN AND METHODS: Brain stem, middle-, and long-latency auditory-evoked responses and evoked otoacoustic emissions were measured in 48 normally hearing IDDM patients and in age- and sex-matched nondiabetic subjects. Peripheral neuropathy was diagnosed by nerve conduction velocity (NCV) at the peroneal and sural nerves. Auditory brain stem responses (ABRs) reflect auditory pathway function within the brain stem; middle-latency responses (MLRs) and long-latency responses (LLRs) originate from the auditory cortex; and evoked otoacoustic emissions (EOAEs) give objective information about preneural, mechanical elements of the cochlear function. RESULTS: A subclinical peripheral neuropathy was found in 12 diabetic patients. We found higher latencies of waves I (t = 4.4, P < 0.0001), III (t = 3.7, P = 0.0004), and V (t = 2.7, P = 0.008) of ABRs in diabetic patients (I: 1.7 +/- 0.13 ms; III: 3.9 +/- 0.17 ms; V: 5.7 +/- 0.24 ms), compared with those of the control group (I: 1.6 +/- 0.13 ms; III: 3.7 +/- 0.18 ms; V: 5.6 +/- 0.17 ms). However, neither central transmission time (i.e., the wave interpeak I-V) nor MLRs and LLRs were found to be significantly different in diabetic and control subjects. Mean EOAE amplitude was found to be significantly reduced (F = 4.2, P = 0.02) in diabetic patients with a reduced NCV (7.6 +/- 3.9 dB; Scheffé test: P = 0.03), but not in those without neuropathy (9.1 +/- 4.2 dB), compared with the control group (10.8 +/- 3.1 dB). No correlations were found between duration of diabetes and EOAEs or between sural NCV and peroneal NCV and metabolic control. EOAEs were not correlated with peroneal and sural NCVs. CONCLUSIONS: Our results indicate that the early preneural dysfunction of cochlear receptors causes a prolonged activation of the peripheral portion of the auditory pathway, while signal conduction along the central auditory pathway was shown to be normal in diabetes.

Adult↗
PubMed1997

Differences in metabolic variables between adult coeliac patients at diagnosis and patients on a gluten-free diet.

BACKGROUND: Coeliac patients often have nutrient malabsorption with nutritional status impairment, but no report on their energy requirements is available. In this study body composition, dietary habits, basal energy expenditure, and substrate oxidation were investigated in patients with the classic form of coeliac disease. METHODS: Sixteen untreated and 18 adult coeliac patients on a gluten-free diet participated in the study. Body composition was assessed by anthropometry and bioimpedance. Energy expenditure was measured by indirect calorimetry. A food diary over 7 days was collected. RESULTS: Coeliac patients showed reduced body weight components but not a different fat-free mass percentage compared with age- and sex-matched healthy volunteers. Basal metabolic rate normalized by fat-free mass (BMR/FFM) was higher in coeliac patients than in controls. Untreated patients showed a significantly higher non-protein respiratory quotient with regard to both treated patients (P < 0.01) and controls (P < 0.05), an increased percentage of carbohydrate intake, and a good correlation between lipid faecal loss and carbohydrate oxidation (Spearman R = 0.74; P < 0.01). CONCLUSIONS: Both groups of patients had lower fat mass and FFM content than controls. The preferential carbohydrate oxidation in untreated patients might be a result of both lipid malabsorption and high carbohydrate intake.

Adolescent↗
PubMed1997

Energy expenditure, substrate oxidation, and body composition in subjects with chronic alcoholism: new findings from metabolic assessment.

There is some controversy as to the effect of ethanol on body weight and alcohol energy contribution to body mass. The aim of this study was to evaluate the effect of alcohol addiction on resting energy expenditure (REE) and body composition. Twelve patients with current alcoholism (A) without severe liver disease or lipid and carbohydrate malabsorption were compared with a group of healthy social drinkers (B) matched for sex, age, and height. Their caloric intake was computed on the basis of a food diary. REE was measured with indirect calorimetry, and body composition was assessed by both anthropometry and bioimpedance. A significant decrease in fat mass in A compared with B was found (14.8 +/- 5.39 vs. 19.0 +/- 3.50 kg; p < 0.05). No significant differences were observed in fat-free mass (FFM) or in total body water between the two groups. A showed higher REE values normalized by FFM than B (35.5 +/- 2.97 vs. 33.0 +/- 2.95 kcal/kgFFM; p < 0.05). The nonprotein respiratory quotient was significantly lower in A than in B (0.76 +/- 0.03 vs. 0.86 +/- 0.03; p < 0.001), and A showed significantly higher lipid oxidation and lower carbohydrate oxidation than B (p < 0.05). The daily caloric intake provided only by food ingestion was found to be significantly higher in controls, but because the percentage of alcohol calories of total energy intake was 46.3 +/- 6.80 in alcoholics and 13.6 +/- 3.59 in controls (p < 0.0001), the total caloric intake, computed as food intake plus alcohol intake, was higher in alcoholics than in control subjects. No statistical differences were found in urinary nitrogen excretion and fecal loss between groups. Patients with alcoholism showed an increased REE over predicted values and a preferential lipid oxidation with respect to controls; these findings could be related to induction of microsomal ethanol oxidizing system and to mitochondrial function adaptation secondary to chronic alcohol abuse. In either case, the effects of such changes in energy metabolism may contribute to alcohol associated hepatic injury.

Adult↗
PubMed1996

Modulation of intrahepatic cholesterol trafficking: evidence by in vivo antisense treatment for the involvement of sterol carrier protein-2 in newly synthesized cholesterol transport into rat bile.

Biliary cholesterol represents one of the two major excretory pathways for sterol elimination from the body and plays a central role in cholesterol gallstone formation. Biliary cholesterol originates from a precursor pool of preformed and newly synthesized free cholesterol. Although it has been suggested that newly synthesized and preformed biliary cholesterol are secreted by independent pathways, the specific cellular and molecular mechanisms are unknown. We used male Wistar rats to study the time-course of the appearance of newly synthesized cholesterol, phosphatidylcholine and protein into bile. The specific role of sterol carrier protein-2 (SCP-2) in the transport of newly synthesized biliary cholesterol was evaluated by an in vivo antisense oligonucleotide approach. In contrast to [14C]phosphatidylcholine and [35S]proteins, the time-course of [14C]cholesterol appearance into bile was rapid, and microtubule- and Golgi-independent. In vivo SCP-2 antisense treatment reduced and delayed the appearance of biliary [14C]cholesterol. Furthermore, hepatic SCP-2 expression increased more than 3-fold over control values in rats that had been treated with diosgenin to increase biliary secretion of newly synthesized cholesterol. These results suggest that SCP-2 is necessary for the rapid transport of newly synthesized cholesterol into bile and that hepatocytes can induce SCP-2 expression according to the rate of biliary secretion of newly synthesized cholesterol.

Animals↗
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

Massive haemobilia after percutaneous liver biopsy in a patient with POEMS syndrome successfully treated by arterial embolization.

A 65-year-old woman with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) developed severe upper right quadrant colic with jaundice, massive haematemesis and melaena following an apparently uncomplicated percutaneous liver biopsy performed for suspected liver involvement. Symptom onset occurred about 18 hours after the procedure. Haemobilia was diagnosed on endoscopic retrograde cholangiopancreatography. An arteriovenous fistula in the third hepatic segment was demonstrated by transfemoral arteriography and successfully embolized using Gelfoam pledgets mixed with Ivalon fragments. A review of percutaneous liver biopsy related haemobilia is presented.

Aged↗
PubMed1996

NA+/K+ ATPase impairment and experimental glycation: the role of glucose autoxidation.

Non enzymatic glycation could be involved in the early impairment of Na+/K+ ATPase that occurs in sciatic nerve of diabetic rats. In fact, decrease of Na+/K+ ATPase activity is one of the first alterations showed in experimental diabetic neuropathy. In this respect, it is known that in the presence of transition metals under physiological conditions, glucose can autoxidize yielding hydrogen peroxide (H2O2) and free radical intermediates, which, in turn, inhibit the cation pump. Our experiments were designed to determine if glucose autoxidation has any relevance in the early steps of Na+/K+ ATPase experimental glycation. Compared experiments with and without the sodium borohydride (NaBH4) reduction step demonstrated that incubation of brain Na+/K+ ATPase with glucose 6-phosphate (G 6-P) and trace metals induced a significant decrease in enzyme activity dramatically enhanced by addition of copper (Cu2+). A concomitant production of H2O2 was noticed. The presence of diethylenetriaminepentaacetic acid (DTPA), a strong metal chelator, completely prevented Na+/K+ ATPase impairment and hydrogen-peroxide formation. No gross structural and conformational alterations of the enzyme can be demonstrated by intrinsic and extrinsic fluorescence measurements. Our results suggest that during the exposure of brain NA+/K+ ATPase to glucose 6-phosphate in vitro (experimental glycation), the decrease in activity can be correlated, at lease in the early phases, to metal-catalyzed production of oxidative species, such as H2O2, through the glucose autoxidation process, and not to glucose attachment to the enzyme. Since plasma hydroperoxides and copper appear to be elevated in diabetic patients with complications, our data suggest a critical role for oxidative reactions in the pathophysiology of the chronic complications of diabetes like neuropathy.

Animals↗
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↗