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Biomedical subjects

A Consoli

Publications and source records attributed to A Consoli.

At least 37 records · Page 2Linked to original sources
PubMed1996

Influence of metabolic control on thromboxane biosynthesis and plasma plasminogen activator inhibitor type-1 in non-insulin-dependent diabetes mellitus.

We have previously shown that tight metabolic control by insulin therapy reduced thromboxane-dependent platelet activation in non-insulin-dependent diabetes mellitus (NIDDM) patients. The present study was undertaken to determine whether a similar effect could be obtained without switching diabetics in secondary failure to insulin treatment. For this purpose, we gave strict diet and exercise advise program and adjusted on a weekly basis the oral antidiabetic therapy (glipizide) that 26 patients with NIDDM had been given over the previous months. Basal measurements of urinary 11-dehydro-TXB2 and PAI-1 confirmed previous findings of enhanced levels of these parameters in NIDDM patients with macrovascular disease in comparison to age- and sex-matched controls. After 2-6 weeks, 16 patients achieved tight metabolic control associated with significant reduction of both thromboxane biosynthesis and PAI-1 levels; 10 patients remained in poor control and no significant decrease of both parameters was observed. We conclude that reduction of in-vivo platelet activation and PAI-1 antigen levels after metabolic improvement obtained by frequent reassessment of sulphonylurea therapy together with strict diet and exercise programs may have beneficial effects on the progression of diabetic micro- and macrovascular disease.

Adult↗
PubMed1996

Giant paraesophageal hernia in an asymptomatic old man. The case for misdiagnosing.

We describe the case of an asymptomatic 66 year-old man with a giant paraesophageal hernia including colonic migration into the chest, responsible for the appearance of a bilateral anterior mediastinal mass on the chest radiograph. We would like to emphasise that this radiologic pattern could lead to misdiagnosing, due to the bilateral air-fluid level in the chest, close to the heart. Pericardial (effusion, cyst), bronchogenic (cyst), as well as esophageal (diverticula) diseases should be considered in the differential diagnosis, although the paucity of symptoms in our patient makes all of these syndromes unlikely to occur. It should also be emphasised that the esophagram can help differential diagnosis between mediastinic organs responsible for the pattern shown in the chest radiograph.

Aged↗
PubMed1995

Regulation of hexokinase II and glycogen synthase mRNA, protein, and activity in human muscle.

Insulin regulates the activity of key enzymes of glucose metabolism in skeletal muscle by altering transcription or translation or by producing activity-altering modifications of preexisting enzyme molecules. Because of the small size of percutaneous muscle biopsies, these phenomena have been difficult to study in humans. This study was performed to determine how physiological hyperinsulinemia regulates the activities of hexokinase (HK), glycogen synthase (GS), and GLUT-4 in human skeletal muscle in vivo. We determined mRNA abundance, protein content, and activities for these proteins in muscle biopsies before and after a hyperinsulinemic clamp in normal subjects. HK I, HK II, GS, and GLUT-4 were expressed in muscle. HK II accounted for 80% of total HK activity and was increased by insulin from a basal value of 2.11 +/- 0.26 to 3.35 +/- 0.47 pmol.min-1.mg protein-1 (P < 0.05); HK I activity was unaffected. Insulin increased GS activity from 3.85 +/- 0.82 to 6.06 +/- 0.49 nmol.min-1.mg-1 (P < 0.01). HK II mRNA was increased 3.3 +/- 1.3-fold (P < 0.05) by insulin infusion. HK I, GS, and GLUT-4 mRNA and protein were unaffected. Because insulin infusion increased HK II but not GS mRNA, we conclude that HK II and GS may be regulated by insulin by different mechanisms in human skeletal muscle.

Adult↗
PubMed1995

Cigarette smoke, ferritin, and lipid peroxidation.

Gas and tar phases of commercially available filter cigarettes were tested for ferritin-iron-releasing effects and polyunsaturated-fatty-acid oxidant capacity in vitro. A vacuum pump-dependent apparatus with Cambridge filters was used to separate gas and tar; the former was directly smoked into reaction mixtures, while the latter was extracted from Cambridge filters in aqueous medium and freshly used at 40 to 80% final concentrations. Both phases induced ferritin iron release, which was not antagonized by superoxide dismutase (SOD). In specific experiments, we have also shown that gas and tar extracts could cross an organic (i.e., chloroform)-phospholipid layer before mobilizing ferritin iron. Once delocalized from ferritin, iron could trigger lipid peroxidation; however, a marked prooxidant effect (inhibited by 20 microM deferoxamine mesylate and significantly decreased by 40 microM vitamin E) was observed only with gas, whereas tar extracts showed antioxidant effects. Accordingly, tar extracts could also antagonize lipid peroxidation driven by non-chelated iron or by peroxyl radicals. In the absence of ferritin, gas-induced lipid peroxidation was very low, and tar extracts were apparently ineffective. Thus, the intrinsic lipoperoxidative capacity of cigarette smoke is low and is due to gas; however, when smoke interacts with ferritin, a marked iron-driven peroxidation becomes manifest essentially with gas, tar components acting as antioxidants. The present data suggest that cigarette-smoke-mediated iron mobilization from ferritin may represent a specific prooxidant mechanism related to cigarette smoking in vivo.

Atmosphere Exposure Chambers↗
PubMed1994

Transmural distribution of antioxidant defences and lipid peroxidation in the rabbit left ventricular myocardium.

The left ventricular subendocardial and subepicardial layers of six perfused rabbit hearts were tested for enzymatic and non-enzymatic antioxidant defences and for lipid peroxidation. The subendocardium showed significantly lower catalase activity and contents of non-protein thiol compounds and vitamin E associated with a higher degree of lipid peroxidation. The activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase showed no significant transmural differences, and Se-independent glutathione peroxidase activity was not detectable in either layer. Comparable results were observed in another group of six unperfused rabbit hearts. In five H2O2-perfused rabbit hearts, lipid peroxidation was higher, and myocardial creatine phosphokinase activity lower, in the subendocardium than in the subepicardium. In this group, only the subendocardium had significantly higher lipid peroxidation levels than the control hearts. Thus, a lower antioxidant capacity and a greater oxidative stress are present in the rabbit subendocardium. These findings could provide insight into the problem of subendocardial vulnerability to free radical-mediated processes, such as occurs in ischaemia-reperfusion injury.

Animals↗
PubMed1994

Hypochlorous acid-induced zinc release from thiolate bonds: a potential protective mechanism towards biomolecules oxidant damage during inflammation.

It has been proposed that metalloprotein zinc mobilization mediated by hypochlorous acid (HOCl) may induce cell injury (see H. Fliss and M. Ménard (1991), Archives of Biochemistry and Biophysics, 287, 175-179). In the present paper, we have demonstrated using a dimercaptopropanol-zinc complex that, once released from thiolate bonds by HOCl, zinc can exert a significant antioxidant effect on both linolenic acid and deoxyribose oxidation induced by iron. In these experimental conditions, however, the antagonism towards deoxyribose oxidation is notably less than that towards linolenic acid peroxidation, thus suggesting a more specific inhibitory effect of zinc on iron-mediated oxidant damage when polyunsaturated fatty acids represent the oxidizable substrate. The antioxidant effects of zinc are strictly related to the "free" form; indeed, the dimercaptopropanol-zinc complex per se is stimulatory even on biomolecules oxidant damage, apparently as a result of the prooxidant prooxidant interaction of the thiol compound with iron. In light of these results, it may be proposed that the zinc released from thiolate bonds by HOCl could specifically limit tissue oxidative burden in pathological conditions involving neutrophil accumulation and activation, such as inflammation and ischemia-reperfusion.

Animals↗
PubMed1993

Dose-response effects of lactate infusions on gluconeogenesis from lactate in normal man.

Lactate is the predominant gluconeogenic precursor in man. To determine the dose-response relationships between plasma lactate concentration and rates of lactate incorporation in plasma glucose (lactate gluconeogenesis, LGN), we infused 17 normal volunteers with sodium lactate for 180 min at rates ranging from 6 to 40 mumol kg-1 min-1 and measured [U-14C]lactate incorporation into plasma glucose, as well as rates of lactate and glucose appearance in plasma. With the highest lactate infusions, plasma lactate increased up to 7 mM (compared to 1.1 +/- 0.13 mM during control sodium bicarbonate infusions, n = 10) and LGN averaged 4.73 +/- 0.23 mumol kg-1 min-1 (compared to 1.57 +/- 0.26 mumol kg-1 min-1 in bicarbonate control experiments, P < 0.001). The data relating plasma lactate concentration to LGN best fit a sigmoidal curve which plateaued at plasma lactate concentrations of approximately 6 mM and yielded an ED50 of 2.04 +/- 0.20 (SD) mM and a Vmax (6.25 +/- 1.2) (SD) (mumol kg-1 min-1). The sum of the basal rate of lactate appearance and the rate of lactate infusion was not significantly different from the overall rates of lactate appearance during the lactate infusions (35.8 +/- 2.2 vs. 34.8 +/- 2.9 mumol kg-1 min-1, P = 0.23). Thus, our results support the view that infusion of exogenous lactate does not suppress endogenous lactate appearance in plasma.

Adult↗
PubMed1993

Differential regulation of intracellular glucose metabolism by glucose and insulin in human muscle.

Insulin and glucose stimulate glucose uptake in human muscle by different mechanisms. Insulin has well-known effects on glucose transport, glycogen synthesis, and glucose oxidation, but the effects of hyperglycemia on the intracellular routing of glucose are less well characterized. We used euglycemic and hyperglycemic clamps with leg balance measurements to determine how hyperglycemia affects skeletal muscle glucose storage, glycolysis, and glucose oxidation in normal human subjects. Glycogen synthase (GS) and pyruvate dehydrogenase complex (PDHC) activities were determined using muscle biopsies. During basal insulin replacement, hyperglycemia (11.6 +/- 0.31 mM) increased leg muscle glucose uptake (0.522 +/- 0.129 vs. 0.261 +/- 0.071 mumol.min-1 x 100 ml leg tissue-1, P < 0.05), storage (0.159 +/- 0.082 vs. -0.061 +/- 0.055, P < 0.05), and oxidation (0.409 +/- 0.080 vs. 0.243 +/- 0.085, P < 0.05) compared with euglycemia (6.63 +/- 0.33 mM). The increase in basal glucose oxidation due to hyperglycemia was associated with increased muscle PDHC activity (0.499 +/- 0.087 vs. 0.276 +/- 0.049, P < 0.05). However, the increase in leg glucose storage was not accompanied by an increase in muscle GS activity. During hyperinsulinemia, hyperglycemia (11.9 +/- 0.49 mM) also caused an additional increase in leg glucose uptake over euglycemia (6.14 +/- 0.42 mM) alone (5.75 +/- 1.25 vs. 3.75 +/- 0.58 mumol.min-1 x 100 ml leg-1, P < 0.05). In this case the major intracellular effect of hyperglycemia was to increase glucose storage (5.03 +/- 1.16 vs. 2.39 +/- 0.37, P < 0.05). At hyperinsulinemia, hyperglycemia had no effect on muscle GS or PDHC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Limitations in the use of [2-14C]acetate for measuring gluconeogenesis in vivo.

This study was undertaken to test two assumptions critical for use of [2-14C]acetate to measure gluconeogenesis in vivo. For the assumption that incorporation into glucose of products of [14C]acetate metabolism does not affect the distribution of label within the glucose molecule, we infused [2-14C]acetate in 17 healthy subjects and [3-14C]lactate in 10 healthy subjects and compared the ratio of the resultant specific activities of plasma glucose carbons 1, 2, 5, 6, and 3, 4 obtained with each tracer. The ratio obtained with [2-14C]acetate (2.99 +/- 0.07) was significantly different from the ratio obtained with [3-14C]lactate, (3.82 +/- 0.2, P < 0.01). Because the model predicts that these ratios should be identical, these results indicate that either the model is incorrect or that metabolism of [14C]acetate to other compounds affects the distribution of the label within the glucose molecule. To test the assumption that plasma 3-OH-butyrate specific activity approximates the specific activity of hepatic intramitochondrial acetyl CoA, we compared the ratio of specific activities of plasma glucose and 3-OH-butyrate obtained in 7 healthy subjects infused with [2-14C]acetate and [2-14C]octanoate. The ratio obtained with [2-14C]acetate (0.18 +/- 0.03) was significantly different from that obtained with [2-14C]octanoate, (0.10 +/- 0.02), P < 0.001. These results suggest compartmentalization of acetyl CoA within liver mitochondria and indicate that plasma 3-OH-butyrate specific activity may not necessarily approximate intramitochondrial acetyl CoA specific activity during [2-14C]acetate infusion. We conclude that assumptions critical for use of [2-14C]acetate to measure gluconeogenesis in vivo are not valid.

3-Hydroxybutyric Acid↗
PubMed1992

[Esophageal achalasia: cardiomyotomy or pneumatic dilatation?].

Sixty-four patients with achalasia of the esophagus were surgically treated during the period 1973-1990. They were analyzed a late follow-up (mean = 78 months) by means of subjective and objective parameters. The Authors emphasize the efficiency of the diagnostic approach so that surgical treatment offers better results. The surgical technique of choice consists of an anterior esophagomyotomy (extending from 6 cm above the esophagogastric junction down to 1-2 cm below it) with the addition of an anterior Dor antireflux procedure through a laparotomy. The other therapeutic approach to achalasia is pneumatic dilatation of lower esophageal sphincter. A retrospective comparison of two different treatments is made through the analysis of the literature (medlars 1986-1990). Relief of dysphagia is reported in 92.78% of patients treated by myotomy and in 78.71% of those treated by forceful dilatation. The morbidity rate is greater after pneumatic dilatation (6% vs 5%) and the mortality rate is 1.1% after myotomy and 0.2% after dilatation. There are not rigorous criteria of choice between the two treatment methods but the Authors indicate that Heller's myotomy with an antireflux procedure achieve better and lasting results.

Adolescent↗
PubMed1992

Skeletal muscle is a major site of lactate uptake and release during hyperinsulinemia.

During conditions of increased glucose disposal, plasma lactate concentrations increase due to an increase in plasma lactate appearance. The tissue sites of the elevated lactate production are controversial. Although skeletal muscle would be a logical source of this lactate, studies using the limb net balance technique have failed to demonstrate a major change in net lactate output when plasma glucose disposal is increased. Because the limb balance technique underestimates production of a substrate when the limb not only produces but also consumes that substrate, we infused 3-14C-lactate basally and during a hyperinsulinemic euglycemic clamp in seven normal volunteers to determine plasma lactate appearance, forearm lactate fractional extraction, and forearm lactate uptake and release. After 3 hours of hyperinsulinemia, glucose and lactate turnovers increased from basal values of 11.8 +/- 0.13 and 12.2 +/- 0.59 to 32.6 +/- 3.4 and 16.5 +/- 1.07 mumol/(min.kg), accompanied by an increase in plasma lactate from 0.88 +/- 0.07 to 1.16 +/- 0.09 mmol/L (P less than .05). Forearm lactate extraction increased from 27% +/- 2% to 38% +/- 2% (P less than .001), resulting in an increase in forearm lactate uptake from 0.65 +/- 0.09 to 1.18 +/- 0.08 mumol/(min.100 mL tissue) (P less than .001). Although forearm lactate net output decreased during hyperinsulinemia, forearm lactate production increased from 1.04 +/- 0.12 basally to 1.69 +/- 0.13 mumol/(min.100 mL). When forearm data was extrapolated to whole body, muscle could account for 41% +/- 4% of systemic lactate appearance basally and 45% +/- 4% during hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Increased lipolysis and its consequences on gluconeogenesis in non-insulin-dependent diabetes mellitus.

The present studies were undertaken to determine whether lipolysis was increased in non-insulin-dependent diabetes mellitus (NIDDM) and, if so, to assess the influence of increased glycerol availability on its conversion to glucose and its contribution to the increased gluconeogenesis found in this condition. For this purpose, we infused nine subjects with NIDDM and 16 age-, weight-matched nondiabetic volunteers with [2-3H] glucose and [U-14C] glycerol and measured their rates of glucose and glycerol appearance in plasma and their rates of glycerol incorporation into plasma glucose. The rate of glycerol appearance, an index of lipolysis, was increased 1.5-fold in NIDDM subjects (2.85 +/- 0.16 vs. 1.62 +/- 0.08 mumol/kg per min, P less than 0.001). Glycerol incorporation into plasma glucose was increased threefold in NIDDM subjects (1.13 +/- 1.10 vs. 0.36 +/- 0.02 mumol/kg per min, P less than 0.01) and accounted for twice as much of hepatic glucose output (6.0 +/- 0.5 vs. 3.0 +/- 0.2%, P less than 0.001). Moreover, the percent of glycerol turnover used for gluconeogenesis (77 +/- 6 vs. 44 +/- 2, P less than 0.001) was increased in NIDDM subjects and, for a given plasma glycerol concentration, glycerol gluconeogenesis was increased more than two-fold. The only experimental variable significantly correlated with the increased glycerol gluconeogenesis after taking glycerol availability into consideration was the plasma free fatty acid concentration (r = 0.80, P less than 0.01). We, therefore, conclude that lipolysis is increased in NIDDM and, although more glycerol is thus available, increased activity of the intrahepatic pathway for conversion of glycerol into glucose, due at least in part to increased plasma free fatty acids, is the predominant mechanism responsible for enhanced glycerol gluconeogenesis. Finally, although gluconeogenesis from glycerol in NIDDM is comparable to that of alanine and about one-fourth that of lactate is terms of overall flux into glucose, glycerol is probably the most important gluconeogenic precursor in NIDDM in terms of adding new carbons to the glucose pool.

Blood Glucose↗
PubMed1992

Role of liver in pathophysiology of NIDDM.

Glucose homeostasis is physiologically maintained by the balance between glucose production by the liver and glucose utilization by the peripheral tissues. Insulin controls hepatic glucose production and promotes glucose utilization by the skeletal muscle. In non-insulin-dependent diabetes mellitus (NIDDM), postabsorptive hepatic glucose production is increased and exhibits a positive correlation with fasting plasma glucose concentration. This increase in hepatic glucose production is the main cause of fasting hyperglycemia in NIDDM. Between the two processes by which the liver produces glucose (gluconeogenesis and glycogenolysis), gluconeogenesis appears to be drastically increased in NIDDM. The increase in gluconeogenesis accounts for most of the increased hepatic glucose production in this condition, and a positive correlation has been found in NIDDM subjects between the rates of gluconeogenesis and fasting plasma glucose concentration. Increased production of gluconeogenic precursors (lactate, alanine, glycerol) fuels this increased gluconeogenesis, but some type of intrahepatic mechanism is also present in NIDDM that increases the hepatic conversion of these substrates into glucose. Hyperglucagonemia and increased hepatic free fatty acid oxidation might be responsible for this increase hepatic gluconeogenic efficiency in NIDDM. Reduced suppression of hepatic glucose production after carbohydrate ingestion also plays an important role in the impairment in postprandial glucose homeostasis in NIDDM. In NIDDM subjects splanchnic extraction of an oral glucose load is not decreased, but hepatic glucose production is suppressed less than in nondiabetic subjects after the load. Residual hepatic glucose production after glucose ingestion is also correlated with fasting plasma glucose in NIDDM. Preliminary data suggest that in the postprandial state increased gluconeogenesis represents the primary mechanism responsible for impaired suppression of hepatic glucose production. Given the primary role of increase hepatic gluconeogenesis in the pathogenesis of hyperglycemia in NIDDM, development of new drugs aimed at correcting the factors that might cause increased gluconeogenesis (e.g., increased free fatty acid oxidation and hyperglucagonemia) might open the way for new form of treatment of this disorder.

Diabetes Mellitus, Type 2↗
PubMed1992

[Primary adenocarcinoma of the appendix].

One case of primary adenocarcinoma of the vermiform appendix is presented. The patient, a 55-year-old man, showed non specific symptoms and the diagnosis was made after surgery. Surgical treatment was right hemicolectomy. The patient is still alive and disease-free 12 months after the operation. The Authors review the literature and discuss some clinical aspects of this rare tumor.

Adenocarcinoma↗