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Biomedical subjects

M Sacchetti

Publications and source records attributed to M Sacchetti.

At least 19 recordsLinked to original sources
PubMed2005

Heterogeneity in limb fatty acid kinetics in type 2 diabetes.

AIMS/HYPOTHESIS: In order to test the hypothesis that disturbances in skeletal muscle fatty acid metabolism with type 2 diabetes are not equally present in the upper and lower limbs, we studied fatty acid kinetics simultaneously across the arm and leg of type 2 diabetic patients (n=6) and matched control subjects (n=7) for 5 h under baseline conditions and during a 4-h hyperinsulinaemic-euglycaemic clamp. METHODS: Limb fatty acid kinetics was determined by means of continuous [U-(13)C]palmitate infusion and measurement of arteriovenous differences. RESULTS: The systemic palmitate rate of appearance was 3.6+/-0.4 and 2.7+/-0.3 micromol.kg lean body mass(-1).min(-1) and decreased during the clamp by 26% (p=0.04) and 43% (p<0.01) in the diabetic patients and in the control subjects respectively. At baseline, palmitate uptake across the arm was similar in the two groups, whereas leg palmitate uptake was lower than in the arm in the diabetic patients. During the clamp, palmitate uptake decreased in the arm (-48%, p=0.02) and the leg (-38%, p=0.04) of the control subjects, whereas it decreased in the arm (-30%, p=0.04) but not in the leg of the diabetic patients. Similarly, during the clamp palmitate release was substantially suppressed in the arm (-47%, p<0.01) and the leg of the control subjects (-45%, p<0.01), but only in the arm of the diabetic patients (-45%, p<0.01). CONCLUSIONS/INTERPRETATION: The present data indicate that type 2 diabetes is characterised by heterogeneity in the dysregulation of skeletal muscle fatty acid metabolism, with only the leg, but not the arm, showing an impairment of fatty acid kinetics at baseline and during a hyperinsulinaemic-euglycaemic clamp causing a physiological increase in insulin concentration.

Arm↗
PubMed2005

Recombinant human interleukin-6 infusion during low-intensity exercise does not enhance whole body lipolysis or fat oxidation in humans.

The present study examined the role of the cytokine IL-6 in the regulation of fatty acid metabolism during exercise in humans. Six well-trained males completed three trials of 120 min of cycle ergometry at 70% peak O(2) consumption (Vo(2 peak); MOD) and 40% Vo(2 peak) with (LOW + IL-6) and without (LOW) infusion of recombinant human (rh)IL-6. The dose of rhIL-6 during LOW + IL-6 elicited IL-6 concentration similar to those during MOD but without altering the circulating hormonal milieu seen in MOD. Palmitate rate of appearance (R(a)), rate of disappearance (R(d)), and oxidation were measured by means of a constant infusion of [U-(13)C]palmitate (0.015 micromol.kg(-1).min(-1), prime NaHCO(3), 1 micromol/kg). Palmitate R(a), R(d), and oxidation were not affected by rhIL-6 infusion, remaining similar to LOW at all times. Palmitate R(a) and oxidation were significantly greater in the MOD trial (P < 0.05) compared with the LOW + IL-6 and LOW trials. Our data show that a low dose of rhIL-6, administered during low-intensity exercise without altering the hormonal milieu, does not alter fatty acid metabolism. These data suggest that the increase in fatty acid utilization seen during exercise at moderate compared with low intensity is not mediated via alterations in plasma IL-6.

Adult↗
PubMed2004

Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro.

To determine whether IL-6 increases lipolysis and fat oxidation in patients with type 2 diabetes and/or whether it exerts this effect independently of changes to the hormonal milieu, patients with type 2 diabetes (D) and healthy control subjects (CON) underwent recombinant human (rh)IL-6 infusion for 3 h. Rates of appearance (Ra) and disappearance (Rd) of [U-(13C)]palmitate and [6,6-(2H2)]glucose were determined. rhIL-6 infusion increased (P < 0.05) palmitate Ra and Rd in a similar fashion in both groups. Neither plasma glucose concentration nor glucose Ra/Rd was affected by rhIL-6 infusion in either group, whereas rhIL-6 infusion resulted in a reduction (P < 0.05) in circulating insulin in D. Plasma growth hormone (GH) was increased (P < 0.05) by IL-6 in CON, and cortisol increased (P < 0.05) in response to IL-6 in both groups. To determine whether IL-6 was exerting its effect directly or through activation of these hormones, we performed cell culture experiments. Fully differentiated 3T3-L1 adipocytes were treated with PBS (control) IL-6, or IL-6 plus dexamethasone and GH. IL-6 treatment alone increased (P < 0.05) lipolysis, but this effect was reduced by the addition of dexamethasone and GH such that IL-6 plus dexamethasone and GH had blunted (P < 0.05) lipolysis compared with IL-6 alone. To assess whether IL-6 increases fat oxidation, L6 myotubes were treated with PBS (Control), IL-6, or AICAR, a compound known to increase lipid oxidation. Both IL-6 and AICAR markedly increased (P < 0.05) oxidation of [(14)C]palmitate compared with Control. Acute IL-6 treatment increased fatty acid turnover in D patients as well as healthy CON subjects. Moreover, IL-6 appears to be activating lipolysis independently of elevations in GH and/or cortisol and appears to be a potent catalyst for fat oxidation in muscle cells.

3T3-L1 Cells↗
PubMed2004

Interleukin-6 and tumor necrosis factor-alpha are not increased in patients with Type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness.

AIMS/HYPOTHESIS: Our aim was to examine the possible direct relationship of interleukin-6 and TNFalpha with insulin sensitivity in humans. METHODS: We carried out two series of euglycaemic-hyperinsulinaemic clamp experiments. In the first (CLAMP1), skeletal muscle mRNA expression and plasma concentrations of IL-6 and TNFalpha were examined in patients with Type 2 diabetes ( n=6), subjects matched for age (n=6), and young healthy (n=11) control subjects during a 120-min supra-physiological hyperinsulinaemic (40 mU.m(-2).min(-1)) euglycaemic clamp. In the second series of experiments (CLAMP2), patients with Type 2 diabetes (n=6) and subjects matched for age (n=7) were studied during a 240-min high-physiological hyperinsulinaemic (7 mU.m(-2).min(-1)) euglycaemic clamp, during which arterial and venous (femoral and subclavian) blood samples were measured for IL-6 and TNFalpha flux. RESULTS: In both experiments the glucose infusion rate in the patients was markedly lower than that in the other groups. In CLAMP1, basal skeletal muscle IL-6 and TNFalpha mRNA were the same in all groups. They were not affected by insulin and they were not related to the glucose infusion rate. In CLAMP2, neither cytokine was released from the arm or leg during insulin stimulation in either group. In both experiments plasma concentrations of these cytokines were similar in the patients and in the control subjects, although in CLAMP1 the young healthy control group had lower (p<0.05) plasma IL-6 concentrations. Using data from all subjects, a strong positive correlation (r=0.85; p<0.00001) was observed between basal plasma IL-6 and BMI. Conversely, a negative relationship (r=-0.345; p<0.05) was found between basal plasma TNFalpha and BMI, although this was not significant when corrected for BMI. When corrected for BMI, no relationship was observed between either basal plasma IL-6 or TNFalpha and GIR. CONCLUSIONS/INTERPRETATION: These data show that the increased circulating IL-6 concentrations seen in patients with Type 2 diabetes are strongly related to fat mass and not insulin responsiveness, and suggest that neither IL-6 nor TNFalpha are indicative of insulin resistance.

Adipose Tissue↗
PubMed2003

Oral theophylline supplementation and high-intensity intermittent exercise.

AIM: The present study was carried out to investigate whether oral theophylline supplementation exerts an ergogenic effect during intermittent high-intensity exercise. METHODS: Ten healthy subjects undertook intermittent exercise (1 min cycling at 120% of VO(2max) with 3 min of recovery until exhaustion). The exercise test was repeated twice, 1 week apart. On each occasion, the subject ingested, in a double blind setting, either theophylline (4.5 mg/kg) or placebo 90 min before commencing the exercise test. RESULTS: Three subjects could not complete both trials due to nausea and dizziness after theophylline had been administered. Time to exhaustion in the remaining subjects was slightly increased after theophylline administration (55.9+/-6 min vs 59.3+/-5.9 min; p<0.05). CONCLUSION: Present data indicate that oral theophylline supplementation delays fatigue onset during intermittent high-intensity exercise. The effect, although statistically significant, does not appear to be marked. The possibility of occurrence of negative side effects and the evidence for its ergogenic potential suggests the necessity to include theophylline in the International Olympic Committee (IOC) World Antidoping Agency (WADA) list as a banned or restricted substance.

Administration, Oral↗
PubMed2002

Human skeletal muscle fatty acid and glycerol metabolism during rest, exercise and recovery.

UNLABELLED: This study was conducted to investigate skeletal muscle fatty acid (FA) and glycerol kinetics and to determine the contribution of skeletal muscle to whole body FA and glycerol turnover during rest, 2 h of one-leg knee-extensor exercise at 65 % of maximal leg power output, and 3 h of recovery. To this aim, the leg femoral arterial-venous difference technique was used in combination with a continuous infusion of [U-(13)C]palmitate and [(2)H(5)]glycerol in five post-absorptive healthy volunteers (22 +/- 3 years). The influence of contamination from non-skeletal muscle tissues, skin and subcutaneous adipose tissue, on FA and glycerol kinetics was studied by catheterization of the femoral vein in antegrade and retrograde directions. Substantially higher net leg FA and glycerol uptakes were observed with a retrograde compared to an antegrade catheter position, as a result of a much lower tracer-calculated leg FA and glycerol release. The whole body FA rate of appearance (R(a)) increased with exercise and decreased rapidly in recovery but stayed higher compared to pre-exercise. The leg net FA uptake decreased immediately on cessation of exercise to near pre-exercise level, but the tracer FA uptake and release decreased slowly and reached constant values after approximately 1.5 h of recovery similar to pre-exercise. Whole body FA reesterification (FA R(d) - FA oxidation; R(d), rate of disappearance) was approximately 400 micromol min(-1) at rest and during exercise, and increased during recovery to 495 micromol min(-1). Leg FA reesterification was 17 micromol min(-1) at rest and decreased to 9 micromol min(-1) during recovery, due to a larger fraction of leg FA uptake being directed to oxidation. A net glycerol exchange across the leg could not be detected under all conditions, but a substantial leg glycerol uptake was observed, which was substantially higher during exercise. Total body skeletal muscle FA and glycerol uptake/release was estimated to account for 18-25 % of whole body R(d) or R(a). IN CONCLUSION: (1) skeletal muscle FA and glycerol metabolism, using the leg arterial-venous difference method, can only be studied if contamination from skin and subcutaneous adipose tissue is prevented; (2) whole body FA reesterification is unchanged when going from rest to exercise, but is increased during recovery; (3) in post-absorptive man total body skeletal muscle contributes 17-24 % to whole body FA and glycerol turnover and FA reesterification at rest; (4) glycerol is taken up by skeletal muscle and the uptake increases many fold during exercise.

Adult↗
PubMed2002

Whole body and leg acetate kinetics at rest, during exercise and recovery in humans.

We have used a constant [1,2-(13)C]acetate infusion (0.12 micromol x min(-1) x kg( 1)) for 2 h at rest, followed by 2 h of one-legged knee-extensor exercise at 65% of leg maximal workload, and 3 h of recovery in six post-absorptive volunteers to quantify whole-body and leg acetate kinetics and determine whether the whole-body acetate correction factor can be used to correct leg substrate oxidation. The acetate whole-body rate of appearance (R(a)) was not significantly different at rest, during exercise or during recovery (365-415 micromol x min(-1)). The leg net acetate uptake was similar at rest and during recovery (approximately 10 micromol x min(-1)), but increased approximately 5-fold with exercise. At rest the leg acetate uptake (approximately 15 micromol x min(-1)) and release (approximately 5 micromol x min(-1)) accounted for 4 and 1.5 % of whole-body acetate disposal (R(d)) and R(a), respectively. When the leg acetate kinetics were extrapolated to the total body skeletal muscle mass, then skeletal muscle accounted for approximately 16 and approximately 6% of acetate R(d) and R(a). With exercise, leg acetate uptake increased approximately 6-fold, whereas leg acetate release increased 9-fold compared with rest. Whole-body acetate carbon recovery increased with time of infusion at rest and during recovery from 21% after 1.5 h of infusion to 45% in recovery after 7 h of infusion. Leg and whole-body acetate carbon recovery were similar under resting conditions, both before and after exercise. During exercise whole-body acetate carbon recovery was approximately 75%, however, acetate carbon recovery of the active leg was substantially higher (approximately 100%). It is concluded that inactive skeletal muscle plays a minor role in acetate turnover. However, active skeletal muscle enhances several-fold acetate uptake and subsequent oxidation, as well as release and its contribution to whole-body acetate turnover. Furthermore, under resting conditions the whole-body acetate correction factor can be used to correct for leg, skeletal muscle, substrate oxidation, but not during exercise.

Acetates↗
PubMed2002

Intramuscular fatty acid metabolism in contracting and non-contracting human skeletal muscle.

The present study was undertaken to investigate the fate of blood-borne non-esterified fatty acids (NEFA) entering contracting and non-contracting knee extensor muscles of healthy young individuals. [U-(13)C]-palmitate was infused into a forearm vein during 5 h of one-legged knee extensor exercise at 40 % of maximal work capacity and the NEFA kinetics, oxidation and rate of incorporation into intramuscular triacylglycerol (mTAG) were determined for the exercising and the non-exercising legs. During 4 h of one-legged knee extensor exercise, mTAG content decreased by 30 % (P < 0.05) in the contracting muscle, whereas it was unchanged in the non-contracting muscle. The uptake of plasma NEFA, as well as the proportion directed towards oxidation, was higher in the exercising compared to the non-exercising leg, whereas the rate of palmitate incorporation into mTAG was fourfold lower (0.70 +/- 0.14 vs. 0.17 +/- 0.04 micromol (g dry wt)(-1) h(-1); P < 0.05), resulting in fractional synthesis rates of 1.0 +/- 0.2 and 3.8 +/- 0.9 % h(-1) (P < 0.01) for the contracting and non-contracting muscle, respectively. These findings demonstrate that mTAG in human skeletal muscle is continuously synthesised and degraded and that the metabolic fate of plasma NEFA entering the muscle is influenced by muscle contraction, so that a higher proportion is directed towards oxidation at the expense of storage in mTAG.

Adult↗
PubMed2002

Complex ventricular arrhythmia induced by overuse of potassium supplementation in a young male football player. Case report.

People practising regular physical activity usually drink hydrosaline beverages. In this study is reported the case of a young football player suffering from premature ventricular beats. He used to take regularly an hydrosaline supplementation which gave him a daily intake of potassium of about 5 g. A stress test on a cycle ergometer showed many monomorphus premature ventricular beats which disappeared when the heart rate was higher than 110 beats/min. Moreover, 3629 polimorphus premature ventricular beats were recorded during a 24 hr ECG monitoring. At the time of the first examination, the plasma potassium concentration was 7,8 mEq x l(-1). The football player was then suspended from practicing sport and he was asked to stop his intake of potassium. The clinical examination was repeated after 3 and 6 months and no ventricular arrhythmias were observed during the stress test as well as during the 24 hours ECG monitoring. The plasma potassium concentration was normal again. The present case report is an example of how the misuse of saline supplementations could result in hyperkalemia and how this condition may lead to ventricular arrhythmias.

Adolescent↗
PubMed2001

Crystal structure prediction for eniluracil.

State-of-the-art molecular modeling tools were used to predict the crystal structure of eniluracil, a compound for which it has not been possible to grow a single crystal. Two methods were used, one that incorporates molecular structure and powder X-ray diffraction data and another that employs molecular structure and lattice energy calculations into the search algorithm. Two structures were identified, one with P2(1)/c and the other with P2(1) symmetry, both of which are consistent with the infrared and Raman spectra. A detailed analysis of the simulated and experimental powder X-ray diffraction patterns indicates that the P2(1)/c structure is the best representation of the crystal structure.

Crystallography, X-Ray↗
PubMed2000

Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6.

1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting skeletal muscle is of such a magnitude that it can account for the IL-6 accumulating in the blood. 2. This was studied in six healthy males, who performed one-legged dynamic knee extensor exercise for 5 h at 25 W, which represented 40% of peak power output (Wmax). Arterial-femoral venous (a-fv) differences over the exercising and the resting leg were obtained before and every hour during the exercise. Leg blood flow was measured in parallel by the ultrasound Doppler technique. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). 3. Arterial plasma concentrations for IL-6 increased 19-fold compared to rest. The a-fv difference for IL-6 over the exercising leg followed the same pattern as did the net IL-6 release. Over the resting leg, there was no significant a-fv difference or net IL-6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL-6 production was 6.8 ng min-1 (kg active muscle)-1 (range, 3.96-9.69 ng min-1 kg-1). 4. The net IL-6 release from the muscle over the last 2 h of exercise was 17-fold higher than the elevation in arterial IL-6 concentration and at 5 h of exercise the net release during 1 min was half of the IL-6 content in the plasma. This indicates a very high turnover of IL-6 during muscular exercise. We suggest that IL-6 produced by skeletal contracting muscle contributes to the maintenance of glucose homeostasis during prolonged exercise.

Adult↗
PubMed1999

Skeletal muscle substrate metabolism during exercise: methodological considerations.

The aim of the present article is to evaluate critically the various methods employed in studies designed to quantify precisely skeletal muscle substrate utilization during exercise. In general, the pattern of substrate utilization during exercise can be described well from O2 uptake measurements and the respiratory exchange ratio. However, if the aim is to quantify limb or muscle metabolism, invasive measurements have to be carried out, such as the determination of blood flow, arterio-venous (a-v) difference measurements for O2 and relevant substrates, and biopsies of the active muscle. As many substrates and metabolites may be both taken up and released by muscle at rest and during exercise, isotopes can be used to determine uptake and/or release and also fractional uptake can be accounted for. Furthermore, the use of isotopes opens up further possibilities for the estimation of oxidation rates of various substrates. There are several methodological concerns to be aware of when studying the metabolic response to exercise in human subjects. These concerns include: (1) the muscle mass involved in the exercise is largely unknown (bicycle or treadmill). Moreover, whether the muscle sample obtained from a limb muscle and the substrate and metabolite concentrations are representative can be a problem; (2) the placement of the venous catheter can be critical, and it should be secured so that the blood sample represents blood from the active muscle with a minimum of contamination from other muscles and tissues; (3) the use of net limb glycerol release to estimate lipolysis is probably not valid (triacylglycerol utilization by muscle), since glycerol can be metabolized in skeletal muscle; (4) the precision of blood-borne substrate concentrations during exercise measured by a-v difference is hampered since they become very small due to the high blood flow. Recommendations are given in order to obtain more quantitative and conclusive data in studies investigating the regulatory mechanisms for substrate choice by muscle.

Arteries↗
PubMed1998

Thermodynamic analysis of moisture sorption isotherms.

This article illustrates how thermodynamic functions can be calculated from moisture sorption isotherms for water-solid systems. The materials evaluated include the drugs albuterol sulfate and indomethacin, the carbohydrates sucrose, raffinose, and trehalose, and the polymers poly(vinyl pyrrolidone) and microcrystalline cellulose. The results demonstrated that significant positive and negative deviations from ideality occurred for water and solid components, respectively, producing higher free energy materials than for the ideal mixtures. The calculations quantitatively discriminated major differences in thermodynamic activity and free energy for all of the solid phases studied, arising from the uniqueness in chemical interactions. This approach to analyzing moisture sorption data is invaluable in advancing our understanding of the physical chemistry of water-solid systems.

Adsorption↗
PubMed1998

[Dual-chamber DDD pacing in NYHA III-IV functional class dilated cardiomyopathy: short and middle-term evaluation].

Effectiveness of dual-chamber pacing in patients with dilated cardiomyopathy is still controversial. Our study was performed: to select the most favorable individual atrioventricular (AV) delay; to compare hemodynamic short-term effects in each patient after 2 periods of DDD pacing and sinus rhythm (AV spontaneous); to assess hemodynamic long-term (1 year) effects after DDD pacing at optimum AV delay. In 1996, 9 patients (7 men, 2 women; mean age 69 +/- 5 years) with dilated cardiomyopathy (5 idiopathic, 4 ischemic), NYHA functional class III-IV, ejection fraction < 30%, end-diastolic volume > 60 ml/m2, mitral regurgitation +2/+3, PR interval > or = 200 ms, were enrolled. All patients were implanted with DDD pacemakers and monitored for: ejection fraction and end-diastolic volume (measured by echocardiography and radionuclide angiography); clinical conditions; exercise tolerance and maximum oxygen consumption (by Weber exercise protocol); neurohormonal activity (plasma renin, aldosterone, atrial natriuretic factor). Data were recorded: before DDD implantation; after 2 randomized, single-blind periods of 3 months in VVI mode (at ventricular "sentinel" rate of 50 b/min) and in DDD mode with the optimum AV delay, corresponding for each patient to the minimum end-diastolic volume measured by radionuclide angiography and to the highest cardiac output recorded by echocardiography; after 6 months of DDD pacing with most favorable AV delay. Three more patients died 6 months after (between sixth and twelfth month of follow-up), due to refractory heart failure; 1 patient dropped out because his pacemaker was programmed in VVI mode at low rate, due to intolerance of DDD pacing. Among the other 4 patients no clinical and laboratory parameters were significantly different after 1 year of follow-up. In conclusion, DDD pacing in selected patients with dilated cardiomyopathy showed disappointing results, despite a strict and laboratory monitoring; DDD pacing could be of major benefit in larger populations, according to Doppler mitral flow pattern: those patients with a larger A-wave amplitude could be more sensitive to DDD pacing than those with evidence of poor atrial systole. Moreover, biatral and/or biventricular pacing could also play a significant role.

Aged↗
PubMed1994

[The surgical treatment of strangulated inguinal-crural hernias in geriatric patients].

The authors describe their own experience relative to 79 patients, aged 70 years or older, who underwent, during three years, emergency surgical intervention for inguinal or crural strangulated hernia. They report a postoperative mortality rate of 8.8% and a postoperative morbidity rate of 40%. They stress the need for timely diagnosis and a meticulous surgical treatment. Therefore, they underline the great importance of the anesthesiologic approach and perioperative intensive care.

Aged↗
PubMed1990

[Diagnostic and prognostic value of CEA and GICA in colo-rectal tumors. A caseload contribution].

The Authors analyse the clinical usefulness of serum levels' determination of Carcinoembryonic Antigen (CEA) and Gastrointestinal Cancer Antigen (GICA) in 152 patients with colorectal cancer, admitted to their Hospital from November 1982 to March 1989. The sensibility for primary diagnosis of each tumor marker is not very high but there is a relationship between the stage and the histological characters of the disease, especially when the markers are considered at the same time. Preoperative serum level determination of CEA and GICA can be considered a good prognostic index: infarct the increase of the levels is generally due to metastatic tissue or local recurrence. This was confirmed during patients follow-up by further tests which revealed recurrence of the disease.

Adenocarcinoma↗