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F Maccari

Publications and source records attributed to F Maccari.

36 records · Page 2Linked to original sources
PubMed1988

Interaction of carnitine with insulin-stimulated glucose metabolism in humans.

To characterize the interactions of carnitine with glucose metabolism, we administered L-carnitine as a primed (3 mmol) constant (17 mumol/min) intravenous infusion to healthy young volunteers during short-term (2 h) euglycemic hyperinsulinemia. In comparison with a control (saline) infusion, exogenous carnitine administration resulted in a stable, fourfold increase in basal serum carnitine levels (160 +/- 14 vs. 36 +/- 2 microM, P less than 0.001). At similar steady-state plasma insulin levels (75 microU/ml), carnitine infusion was associated with a 17 +/- 3% stimulation of whole body glucose utilization (6.56 +/- 0.60 vs. 5.57 +/- 0.44 mg.min-1.kg-1, P less than 0.001). This effect was more pronounced in the subjects with higher rates of glucose disposal (r = 0.65, P less than 0.05). Net rates of insulin-induced glucose oxidation (measured by continuous, computerized indirect calorimetry) were similar with or without carnitine (1.67 +/- 0.23 vs. 1.65 +/- 0.10 mg.min-1.kg-1, respectively). As a consequence, the carnitine-induced enhancement of total glucose metabolism was quantitatively accounted for by a 50% increase in nonoxidative glucose disposal (2.89 +/- 0.81 vs. 1.92 +/- 0.51 mg.min-1.kg-1, P less than 0.05). The inhibitory effect of insulin on net lipid oxidation was not altered by carnitine (-0.67 +/- 0.09 vs. -0.62 +/- 0.06 mg.min-1.kg-1). Circulating levels of free fatty acids (FFA), glycerol, and beta-hydroxybutyrate fell in parallel during insulin infusion in the test and control study, and blood lactate concentrations rose by similar amounts (approximately 0.35 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Plasma and urine pharmacokinetics of free and of short-chain carnitine after administration of carnitine in man.

To 6 healthy volunteers 30 mg/kg of L-carnitine (1,3-hydroxy-4-N-trimethylamino-butyrate) were injected intravenously and plasma levels (mumol/l) of free and short-chain carnitine were determined at different times between 0.033 and 24 h. The urinary excretion of L-carnitine and short-chain carnitine in 24 h was also measured. After a period of wash-out the subjects received 100 mg/kg of L-carnitine orally and plasma levels were determined between 0.5 and 24 h. The urinary excretion of L-carnitine was measured for a period of 18.5-33 h after treatment. 3 of the volunteers also received 30 mg/kg of L-carnitine orally. Carnitine plasma levels were determined at different times between 0.5 and 18 h, while the urinary excretion of L-carnitine was measured for 48 h following the treatment. The results could indicate the presence of saturation phenomena in the absorption process for the oral doses used; specific research is required to ascertain this phenomena. The transfer of carnitine from central to extravascular volume is relatively rapid, as is its urinary excretion. The short half-life of carnitine and acetyl-carnitine can suggest the use of new forms of administration (slow-release).

Administration, Oral↗
PubMed1987

The effect of exogenous L-carnitine on biochemical parameters in serum and in heart of the hyperlipidaemic rat.

In previous experiments we have demonstrated that L-carnitine administration is capable of reducing olive oil-induced lipidaemia in the rat. In the present study we determined the effect of L-carnitine on the levels of (acyl)carnitines in heart and serum in addition to its effect on serum levels of lipids and ketone bodies after olive oil gavage feeding. L-carnitine was found to reduce the level of myocardial long-chain acylcarnitine which was increased by the olive oil treatment. It also increased the levels of carnitine and acid soluble acylarnitines in both heart and serum. L-carnitine administration caused a clearcut decrease of olive oil-induced lipidaemia and ketonaemia. These effects of added L-carnitine strongly suggest that the stimulation of the beta-oxidation in the mitochondria (at the expense of extra mitochondrial triglycerceride synthesis) is suboptimal after fat loading.

Animals↗
PubMed1987

L-carnitine effect on plasma lipoproteins of hyperlipidemic fat-loaded rats.

The effect of oral L-carnitine administration to rats fed olive oil has been studied. Carnitine significantly decreased triglyceride, cholesterol and phospholipid levels. Particularly, the levels of chylomicron and very low density lipoproteins in the blood were lowered. Low density lipoprotein levels were not affected, and high density lipoproteins were found to be decreased by 20%. Because carnitine did not change the composition of chylomicron and very low density lipoproteins fraction or affect the gastrointestinal triglyceride residue (about 1/3 of the original load), an effect of carnitine on hepatic fatty acid handling is most likely. The lowering of plasma free fatty acid levels by carnitine administration is in favor of an effect of carnitine on fatty acid handling. The effect on the liver is illustrated by the study of acetoacetate formation in in vitro perfused livers from previously olive oil loaded +/- carnitine-treated rats. Carnitine pretreatment stimulated ketogenesis. It is speculated that carnitine administration, by promoting beta-oxidation, lowers the production of very low density lipoproteins. This may be accomplished partly by an increase in the hepatic level of fatty acid binding protein, which also has been observed.

Animals↗
PubMed1987

Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects.

Raised levels of free fatty acids (FFA) compete with glucose for utilization by insulin-sensitive tissues, and, therefore, they may induce insulin resistance in the normal subject. The influence of experimental elevations in FFA levels on glucose metabolism in native insulin-resistant states is not known. We studied seven women with moderate obesity (63% above their ideal body weight) but normal glucose tolerance with the use of the insulin clamp technique with or without an infusion of Intralipid + heparin. Upon raising plasma insulin levels to approximately 60 microU/mL while maintaining euglycemia, whole body glucose utilization (3H-3-glucose) rose similarly without (from 66 +/- 7 to 113 +/- 11 mg/min m2, P less than .02) or with (from 70 +/- 7 to 137 +/- 19 mg/min m2, P less than .02) concomitant lipid infusion. In contrast, endogenous glucose production was considerably (73%) suppressed (from 66 +/- 7 to 15 +/- 8 mg/min m2, P less than .001) during the clamp without lipid, but declined only marginally (from 70 +/- 7 to 48 +/- 7 mg/min m2, NS) with lipid administration. The difference between the control and the lipid study was highly significant (P less than .02), and amounted to an average of 3.8 g of relative glucose overproduction during the second hour of the clamp. Blood levels of lactate rose by 34 +/- 15% (.1 greater than P greater than .05) in the control study but only by 17 +/- 10% (NS) during lipid infusion. Blood pyruvate concentrations fell in both sets of experiments (by approximately 45% at the end of the study) with similar time courses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Protection by acyl-carnitines and phenylmethylsulfonyl fluoride of rat heart subjected to ischemia and reperfusion.

Perfusion of rat hearts according to the Langendorff technique with micromolar concentrations of palmitoylcarnitine or millimolar concentrations of phenylmethylsulfonyl fluoride protect the heart from deterioration by reperfusion after total-ischemia. This is based on the retention of the cytosolic enzymes determined (lactate dehydrogenase, glycogen phosphorylase and glycogen synthase) and of myoglobin, as well as on the resumption of contractile activity. Palmitoylcarnitine, like phenylmethylsulfonyl fluoride, could protect through plasma membrane stabilization, since more hydrophilic compounds had no effect.

Animals↗
PubMed1985

The effect of exogenous L-carnitine on fat diet-induced hyperlipidemia in the rat.

In rats receiving a fat diet (75% Altromin R and 25% olive oil) ad libitum for 15 hours, an orally administered dose of 500 mg/kg L-carnitine produces: an increase in serum carnitine and acetyl-carnitine levels; a decrease in serum triglyceride (TG) and free fatty acid (FFA) levels; a normalization of the heart and liver carnitine pattern; a reduction of myocardial neutral lipase (NL) activity, without affecting lipoprotein lipase (LPL) of the heart. Under these experimentally-induced conditions, L-carnitine stimulates the excretion of acyl groups as acyl-carnitines with the urine. Acylcarnitines are practically absent from the urine of control animals.

Acetylcarnitine↗
PubMed1983

Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients.

A group of 14 uremic patients on intermittent hemodialysis was admitted to a cross-over double-blind trial in order to evaluate serum and muscle carnitine levels before and after 60 days of L-carnitine oral (2 g/day) treatment. The morphology of muscle fragments was studied by light and electron microscopy. Symptoms (asthenia, cramps) occurring during hemodialysis were also recorded. After L-carnitine treatment the blood and muscle levels of the metabolite increased simultaneously to reduced asthenia and cramps. Morphological examination of the muscle of 13 of 14 patients did not reveal any pre- or posttreatment pathological alterations. The presence of nemaline rods was morphologically diagnosed in only one case and was no longer observed at the second biopsy at 2 months of L-carnitine treatment.

Adult↗
PubMed1983

Plasma and muscle carnitine levels in haemodialysis patients with morphological-ultrastructural examination of muscle samples.

The present study investigates 14 patients on intermittent haemodialysis. Pre-dialysis blood and muscle samples taken for determining plasma free- and acetylcarnitine levels. The tissue fragments were used for light and electron microscopy studies. Our results support the findings of other investigators that patients on haemodialysis generally display decreased free- and acetylcarnitine levels both in plasma and skeletal muscle when compared with control values. Muscle carnitine deficiency was apparently more severe in the longer-term haemodialysis patients. Moreover, a significant correlation (p less than 0.05) between plasma and muscle free-carnitine values was found. Morphologically no pathological alterations were observed in the muscle fibres in 13 of the patients. Light and electron microscopic studies of the muscle fibre of the 14th patient showed a typical nemaline myopathy with rod bodies in the cytoplasm. The muscle free-carnitine concentration in this patient was among the lowest of the group.

Adult↗
PubMed1982

The effect of excess (acyl) carnitine on lipid metabolism in rat heart.

During Langendorff perfusion of rat hearts with Intralipid, the resulting fat accumulation in the hearts can be inhibited by the addition of 5 mM L-carnitine to the perfusion medium. The mechanism of this phenomenon is probably the inhibition of lipid accumulation in the heart by acylcarnitine rather than stimulation of fatty acid oxidation by excess carnitine addition. Palmitoylcarnitine was found to stimulate trioleoylglycerol hydrolysis at neutral pH in heart homogenates, when it was tested in the presence of relatively much protein. At higher palmitoylcarnitine: protein ratios, however, lipolysis was inhibited. Inhibition of lipolysis was also observed in lipid-enriched hearts during retrograde perfusion by the addition of 5 mM carnitine suggesting that also in intact heart long-chain acylcarnitine excess may inhibit lipolytic activity.

Animals↗
PubMed1982

In vivo and in vitro antilipolytic effects of some various substituted homocysteine-thiolactone-nicotinamides: structure-activity study.

The antilipolytic activity of homocysteine-thiolactone-nicotinamide (ST22) and in 2-chloro (ST71), 6-chloro (ST82) and 6-hydroxy (ST90) derivatives was investigated by evaluation of serum free fatty acids (FFA) and triglycerides (TG) (in vivo) and FFA release from adipose tissue (in vitro). Increased FFA levels in 17-hr fasted rats at 60 min following treatment with 7 . 10(-4) mol kg-1 p.o. were reduced by 70% (ST22), 60% (ST82) and 18% (ST71), whereas ST90 provoked no change; TG levels showed similar changes. Basal FFA release from epididymal rat adipose tissue at 60 min following treatment with 7 . 10(-4) mol kg-1 p.o. of ST22 and ST82 was reduced by 79 and 45%, respectively. Lipid mobilization induced by noradrenaline (NA) was diversely affected by the compounds according to the tests employed: with in vivo experiments, serum FFA levels were reduced by 60, 70, 10 and 5% at 60 min following treatment with ST22, ST82, ST71 and ST90, respectively (7 . 10(-4) mol kg-1 p.o.; NA bitartrate, 2 mg kg-1 s.c.); in vitro, ST22 produced no change, whereas the other compounds induced a significant mobilization of FFA. The results suggest that: (a) antilipolytic activity can be greatly modified when various substituents capable of influencing either the inductive (-I) or the resonance (+M) effect are introduced into the different positions of the pyridine ring; and (b) the lipolysis experiments did not evince any direct relationship between the effects obtained by the in vivo tests and those obtained by the in vitro tests.

Adipose Tissue↗
PubMed1981

Antagonism of doxorubicin cardiotoxicity by carnitine is specific of the L-diasteroisomer.

The therapeutic use of Doxorubicin in the treatment of human solid tumors is restricted because of its cardiotoxicity. It has been demonstrated that D,L-Carnitine reduces or suppresses some of the cardiotoxic effects produced by the antibiotic. The results of this study, carried out on rat heart Langendorff preparation show that the decrease in heart rate, coronary flow, and contractile force, occurring after Doxorubicin infusion, was antagonized by the laevo-diasteroisomer; the dextroform was totally inactive. On the contrary, both forms increased phospholipid concentration in the myocardium. This would suggest that the reparatory effect of L-Carnitine against Doxorubicin cardiotoxicity is linked to the natural role played by this substance in metabolic processes.

Animals↗
PubMed1978

[Variable behavior of urinary hydroxyproline in breast cancer with osseous metastases].

Serial estimations of the hydroxyproline (OHP) excretion during chemotherapy were performed in 24 women bearing advanced breast carcinoma with skeletal metastases. There was a significant correlation between sensitivity of the metastases to treatment and OHP content of urine. Many factors, including age of patients, type, number and extent of metastases, don't influence OHP excretion. The estimation of the urinary OHP levels, with the changes after antiblastic treatment, can be useful in prognostic evaluation of the metastatic breast cancer.

Adult↗
PubMedDate not supplied

Risk factors for psoriasis: a retrospective study on 501 outpatients clinical records.

Possible risk factors for psoriasis were studied by means of a retrospective evaluation of epidemiological and clinical features in 472 clinical records of outpatients affected by plaques psoriasis. We calculated the relation between the categorical variables with chi-squares contingency table analysis (with Yates correction) and odds ratio (O.R.) from the two variables with their respective confidence intervals at 95%. Among patients 267 were men (57%) and 205 women (43%); the mean age was 46.5+/-16.7 years, with no differences in sex. A significant relationship was found between age at onset < or =40 years and familiarity for psoriasis (p<0.0001-O.R.=2.71, C.I..95%: 2.12-3.48). The percentage of men with extensive lesions (extension >30%) was significantly higher than of women (p<0.05-O.R.=1.60, C.I..95%:1.35-1.90). Moreover, a significant association between extension of lesions and BMI was detected (p<0.0107-O.R.=2.10, C.I.95%:1.33-3.30) and the strength of this relation was assessed using the linear regression test. Mean age at onset was significantly lower in patients systemically treated (p<0.0003-O.R.=2.61, C.I.95%: 1.69-4.04). The results obtained can provide the basis for a standard clinical record, including data for a prospective study that may confirm the relation between psoriasis and some risk factors.

Adolescent↗