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Biomedical subjects

M Zoli

Publications and source records attributed to M Zoli.

At least 217 records · Page 12Linked to original sources
PubMed1982

Branched-chain amino acids and alanine as indices of the metabolic control in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients.

Alterations in plasma branched-chain amino acids (valine, isoleucine and leucine) and alanine have been described in patients with insulin-dependent diabetes mellitus who have poor metabolic control. To assess the relevance of these abnormalities as indices of metabolic control, we sequentially evaluated plasma amino acids in 14 poorly controlled diabetics (seven Type 1 (insulin-dependent) and seven Type 2 (non-insulin-dependent) patients) until good control was achieved. The sum of branched-chain amino acids in both groups of uncontrolled diabetic patients was significantly increased compared with the values for the same subjects in good metabolic control. No statistically significant differences were present between ketotic and non-ketotic uncontrolled patients. The amelioration of the diabetic state with either insulin treatment or oral hypoglycaemic agents, reduced progressively branched-chain amino acids. The sum of valine, isoleucine and leucine strictly correlated with daily urinary glucose (r = 0.73), but less well with fasting blood glucose (r = 0.43), non-esterified fatty acids (r = 0.46) and glycosylated haemoglobin (r = 0.38). Alanine did not show any statistically significant differences at various stages of diabetic control. Branched-chain amino acids, but not alanine, may be used as indices of short-term diabetic control.

Alanine↗
PubMed1982

Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis.

The contribution of hyperammonemia to plasma amino acid imbalance in patients with liver disease was assessed in 10 subjects with chronic hepatitis and in 17 advanced cirrhotics. Insulin, glucagon, and plasma amino acids were determined both in the basal state and 45 min after oral ammonium chloride, at doses used in the ammonia-tolerance test. In cirrhotics, ammonia increased to 3 times basal values, in association with a rise in insulin and, more marked, in glucagon. Aromatic amino acids and free tryptophan further increased, while a significant fall in branched-chain amino acids and glutamate was observed. The increase in ammonia levels strongly correlated with the increase in glucagon (r = 0.707). Two patients, with large esophageal varices, showed signs of disturbed consciousness, in association with a marked rise in ammonia and in the ration of free tryptophan to the sum of neutral amino acids. In patients with chronic hepatitis, whose ammonia levels rose slightly, minor variations in pancreatic glucoregulatory hormones and plasma amino acids were observed, as also happened in 10 healthy subjects following ammonium chloride ingestion. Our data fit with the hypothesis that the plasma amino acid imbalance of cirrhotics may be partly due to ammonia-induced changes in pancreatic hormones.

Adult↗
PubMed1982

Myofibrillar protein catabolic rates in cirrhotic patients with and without muscle wasting.

1. The urinary excretion of 3-methylhistidine and creatinine was measured in 15 controls and in two groups of 15 patients with liver cirrhosis, with and without severe muscle wasting. All subjects were on a meat-free diet. The values obtained were used to calculate the fractional catabolic rate of myofibrillar protein. 2. In patients without muscle wasting 3-methylhistidine excretion was high in the presence of normal urinary creatinine. The fractional breakdown rate was significantly increased as compared with that of controls. 3. In patients with severe muscle wasting 3-methylhistidine excretion was normal and urinary creatinine was remarkably reduced. The myofibrillar catabolic rate was further increased compared with that of controls and of the other group of patients. 4. 3-Methylhistidine and creatinine excretion allow a complete evaluation of myofibrillar protein degradation, which appears to be remarkably increased in cirrhotic patients. The relevance of increased myofibrillar protein turnover in muscle wasting of subjects with advanced cirrhosis remains to be determined.

Adult↗
PubMed1982

New vistas on synaptic plasticity: the receptor mosaic hypothesis of the engram.

The concepts of coexistence of transmitters and of receptor-receptor interactions have increased our understanding of the integrative processes regulating synaptic homeostasis and synaptic plasticity. Depending upon the ionotropic or metabotropic characteristics of the cotransmitter, it may be mainly involved in synaptic homeostasis or synaptic plasticity, respectively. A chemical trace of the postsynaptic activity can be obtained because of the plasticity of the receptor molecules. Thus, the heuristic hypothesis is introduced that islands of receptors located on postsynaptic membranes of local circuits can be formed by means of receptor-receptor interactions favouring ordered electrotonic sequences in the local circuits. This hypothesis has been named the receptor mosaic hypothesis of the engram. The islands or clusters of receptors can then store specific and complex information and when activated by the transmitters they may induce unique changes in ion permeability and cell metabolism which, at the local circuit level, can mimic exactly a previous electrotonic sequence. They can therefore represent at least part of the engram. This hypothesis is introduced against the background of the possible existence of different types of encodings of memory.

Animals↗
PubMed1981

Relevance of HBe/anti-HBe system and DNA polymerase activity in chronic hepatitis-B virus carriers on haemodialysis. A prospective study.

To assess the relevance of HBe/anti-HBe system and DNA polymerase activity in patients on regular dialysis treatment, we prospectively studied 38 patients on haemodialysis, who were chronic carriers of HBs Ag (range 6-66 months), and 26 HBs Ag negative dialysis patients as controls. HBe Ag was present in 74%, DNA polymerase in 60%, and anti-HBe in 13% of HBs Ag positive patients. After a mean follow-up of 23.5 months, only 2 patients, who had been HBe Ag positive, had cleared HBs Ag, and 1 of them had turned to anti HBs positivity. Among the patients who were still HBs Ag positive, only 1 had lost HBe Ag, without developing anti-HBe. Throughout the study, SGOT and SGPT levels were significantly raised in HB virus carriers as compared to controls. In the HBs Ag positive group, the presence of HBe Ag and/or DNA polymerase characterized a subgroup with the most striking abnormalities in enzyme levels. The caused of death in the HBs Ag positive group were not related to liver disease. Viral replication usually takes place in HB virus carrier state, and the underlying liver disease, are not major problems at present in patients on chronic haemodialysis.

Adolescent↗
PubMed1981

Plasma amino acids as markers of liver dysfunction in cirrhotics.

To determine the role of liver dysfunction in the plasma amino acid profile of cirrhotic patients, we correlated basal plasma amino acids and several biochemical and functional hepatic variables in 29 cirrhotics with normal mental state or mild encephalopathy. Increased levels of aromatic amino acids and free tryptophan correlated positively with the extent of portosystemic shunt, as assessed by the ammonia tolerance test (r = 0.758 and r = 0.589, respectively). There was a negative correlation between these amino acids and liver function, as evaluated by the galactose elimination capacity test (r = -0.657 and r = -0.551), thus suggesting that phenylalanine, tyrosine, and free tryptophan may be considered indexes of liver dysfunction in non-comatose cirrhotics.

Adult↗
PubMed1981

Binding of tryptophan to albumin in liver cirrhosis: a reappraisal of the problem.

The competition of free fatty acids and bilirubin in the binding of tryptophan to albumin was studied in 12 controls and 36 cirrhotics at various stages of hepatic encephalopathy. Total tryptophan was not significantly altered in cirrhotics, while free tryptophan progressively increased with the deterioration of their mental state. Bound tryptophan levels were consequently reduced in patients with cirrhosis, mainly in the presence of hepatic encephalopathy, and strictly correlated with albumin (r = 0.80). The ratio bound tryptophan/albumin, which represents the muMoles of tryptophan bound by 1 gram of albumin, did not show significant difference in the various groups of patients. No correlation was found between this ratio and the levels of free fatty acids and bilirubin, which were raised in cirrhotics. Our data suggest that the fall in albumin levels, but not the increase in free fatty acids or bilirubin, may play a role in increasing free tryptophan levels in cirrhotics. Thus, marked hypoalbuminemia may be a risk factor of hepatic encephalopathy in patients with cirrhosis.

Albumins↗
PubMed1980

Prevalence of subclinical hepatic encephalopathy in cirrhotics and relationship to plasma amino acid imbalance.

Neuropsychological status, as assessed by trailmaking test; plasma amino acids, and ammonia, were studied in 54 cirrhotics without clinical evidence of encephalopathy to determine the prevalence of subclinical mental dysfunction and its relationship to metabolic abnormalities. Control values for psychometric performance were established in 54 normal subjects matched for age, sex, educational level, and employment status. Of these subjects, 16 were also used as controls for fasting ammonia and plasma amino acids. Eighteen cirrhotics (33%) showed impaired performances of the psychometric test; free tryptophan and the ratio free tryptophan to neutral amino acids were increased in 37% and 62% of cases and correlated with the psychometric scores (r = 0.45 and r = 0.70, respectively). In eight cirrhotics with mild encephalopathy, psychometric and metabolic evaluations were repeated several times during the infusion of amino acid solutions rich in branch-chain amino acids. Again significant correlations were observed between the psychometric scores and plasma amino acids. We conclude that a considerable proportion of clinically normal cirrhotics have neuropsychological deficits. The severity of impairment may be related to the plasma amino acid imbalance, namely to an increased passage of tryptophan across the blood-brain barrier.

Adult↗
PubMed1979

Insulin and glucagon levels in liver cirrhosis. Relationship with plasma amino acid imbalance of chronic hepatic encephalopathy.

Alterations in insulin and glucagon levels might account for the plasma amino acid imbalance of cirrhotics. In order to verify this hypothesis we evaluated basal insulin, glucagon, branched-chain amino acids, aromatic amino acids, and free tryptophan in 13 controls and 37 cirrhotics divided on the basis of their mental state; in 4 patients the hormonal and amino acid patterns were sequentially studied during various stages of encephalopathy. Glucagon is high in cirrhotics and progressively increases with the worsening of the mental state. Free tryptophan and aromatic amino acids show a similar behavior and significantly correlate with glucagon levels (r = 0.67 and r = 0.81, respectively). On the other hand insulin levels, which are high in cirrhotics without encephalopathy, fall in the presence of deep coma. Insulin did not correlate with any of the plasma amino acids considered. Our data suggest that the catabolic state associated with increased glucagon levels may account for some of the alterations in the plasma amino acid profiles of cirrhotics. Portal-systemic shunting does not seem to be the common cause of both hyperglucagonemia and hyperaminoacidemia. Decreased branched-chain amino acid levels may be related to factors different from those involved in the alterations of carbohydrate homeostasis.

Adult↗
PubMed1979

The role of insulin and glucagon in the plasma aminoacid imbalance of chronic hepatic encephalopathy.

Increased glucagon (IRG) levels have been documented in liver cirrhosis, particularly associated with portal-systemic shunting. In spite of increased insulin (IRI) levels, IRI/IRG are reduced. This alteration has been proposed to have a pathogenic role in plasma aminoacid imbalance which seems to account for hepatic encephalopathy. We studied IRG and IRI/IRG in 13 controls and in 3 groups of cirrhotics, divided on the basis of their mental state. Glucagon was determined by means of 30 K Unger's antibody; insulin by a double antibody technique. Results are expressed in the table as means +/- SEM. (Formula: see text)A progressive increase in IRG secretion is present in cirrhotics and correlates with the mental state; IRI/IRG is not altered in cirrhosis until neurological distrubances are present. A relative fall in IRI which can no more balance the increasing IRG values characterizes hepatic encephalopathy.

Amino Acids↗
PubMed1979

Oral glucose in cirrhotics. Effects on plasma aminoacid patterns and the role of insulin and glucagon.

Changes in the plasma aminoacid (AA) profile present in hepatic encephalopathy were related to a catabolic state characterized by a reduced insulin/glucagon molar ratio (IRI/IRG). Oral glucose is able to suppress the hyperglucagonemia and further to increase the elevated insulin levels of cirrhotics leading to a rise of IRI/IRG. We evaluated the plasma AAs in ten controls and twelve cirrhotics following the ingestion of oral glucose. At 180 min we demonstrated a similar fall (about 35%) of plasma AAs both in cirrhotics and in controls, with the exception of free tryptophan, which fell more markedly in cirrhotics (about 60%), possibly secondary to the fall in plasma free fatty acids. After the oral glucose load, the levels of aromatic AAs and free tryptophan, as well as the molar ratio free tryptophan/branched-chain + aromatic AAs returned to normal in cirrhotics. High levels of both aromatic AAs and free tryptophan have been implicated in the pathogenesis of hepatic coma. Our data support the hypothesis that the administration of oral glucose might be relevant in the management of cirrhotic patients with hepatic encephalopathy, possibly improving their mental state.

Adult↗
PubMedDate not supplied

Muscle protein breakdown in liver cirrhosis and the role of altered carbohydrate metabolism.

The rates of muscle protein breakdown, as estimated by the urinary excretion of 3-methylhistidine, were assessed in 30 cirrhotics and 15 controls on a strictly controlled diet. 3-Methylhistidine excretion was increased in cirrhotics irrespective of the etiology of the disease, and correlated with basal glucagon levels and with the insulin/glucagon ratio. In nine cirrhotics and nine age- and sex-matched controls, similar correlations were found between 3-methylhistidine and the areas under 24-hr glucagon or insulin/glucagon curves. A larger amount of 3-methylhistidine was excreted during the nighttime than during the daytime, when glucagon secretion was suppressed and the insulin/glucagon ratio was increased. It is concluded that muscle protein catabolism is increased in cirrhotics, possibly as a result of hyperglucagonemia or the reduced insulin/glucagon ratio. These data agree with the clinical observation of a progressive reduction in lean body mass which becomes evident in an advanced stage of the disease.

Adult↗
PubMedDate not supplied

Anticatabolic effect of branched-chain amino acid-enriched solutions in patients with liver cirrhosis.

An amino acid mixture rich in branched-chain amino acids and poor in aromatic amino acids was infused in six cirrhotics with altered plasma amino acid profile and normal mental state. The effect on muscle protein catabolism, as measured by urinary excretion of 3-methylhistidine, was assessed during two consecutive 3-day period in which patients received the amino acid mixture alone or in a hypertonic dextrose solution. During a 3-day basal period, cirrhotics showed increased rates of 3-methylhistidine excretion as compared to six matched healthy subjects. Both treatments reduced urinary 3-methylhistidine to normal. During treatment, branched-chain amino acids failed to normalize, plasma aromatic amino acid concentrations and ammonia declined, and alanine increased. Branched-chain amino acids are mainly oxidized in skeletal muscle with production of alanine. Reduced muscle protein catabolism following amino acid infusion is consistent with the physiological role of branched-chain amino acids in suppressing protein breakdown and stimulating protein synthesis. Long-term therapy with branched-chain amino acid-enriched mixtures may prove useful in advanced cirrhotics with severe muscle wasting.

Adult↗
PubMedDate not supplied

Effect of euglycemic insulin infusion on plasma levels of branched-chain amino acids in cirrhosis.

To test the hypothesis that hyperinsulinism is responsible for reduced branched-chain amino acids in cirrhotics, plasma amino acids were sequentially determined in 8 controls and 8 matched cirrhotics during continuous i.v. insulin infusion. An artificial endocrine pancreas which infused glucose was used to sustain euglycemia. Basal plasma insulin levels were high and branched-chain amino acids were reduced in cirrhotics. Insulin infusion raised insulin levels to 3 to 4 times basal values. During the test, the decline in branched-chain amino acids was markedly higher in controls who had similar steady-state insulin levels. Not only did the level of branched-chain amino acids in controls reach the values seen in cirrhotics after 60 min, but the levels continued to fall at a significantly higher rate throughout the second hour. Glucose consumption and the ratio of glucose infused/steady-state insulin--a measure of tissue sensitivity to insulin--were markedly reduced in cirrhotics and positively correlated with the decline in branched-chain amino acids. In cirrhotics, insulin effects on carbohydrate and branched-chain amino acid metabolism were reduced. Low branched-chain amino acid levels in cirrhotics are not likely to depend only on hyperinsulinism.

Adult↗
PubMedDate not supplied

Portal venous flow in response to acute beta-blocker and vasodilatatory treatment in patients with liver cirrhosis.

The drugs currently under investigation in the prevention of recurrent gastrointestinal bleeding in cirrhosis are likely to decrease the portal pressure by means of a primary reduction of portal blood flow. The hemodynamic effects of beta-blocking agents and vasodilatory drugs were noninvasively measured in eight patients with cirrhosis by means of pulsed echo-doppler equipment. Portal caliber, blood velocity and flow were recorded hourly after a single dose of propranolol (40 mg p.o.) or atenolol (100 mg p.o.), and every 5 min after treatment with isosorbide dinitrate (5 mg sublingually). The drugs were administered at random with an interval of 2 days or more. The portal caliber decreased after atenolol, but did not change after propranolol and isosorbide. The blood velocity decreased by 29 +/- 2% 3 hr after propranolol, by 26 +/- 2% 3 hr after atenolol and by 31 +/- 3% 15 min after isosorbide. The portal blood flow decreased by 0.29 +/- 0.03 liters per min after propranolol, by 0.34 +/- 0.06 after atenolol and by 0.26 +/- 0.03 after isosorbide, without any difference among the various treatments. beta-blockers and vasodilatory drugs have comparable effects on portal blood flow. beta 1-selective and nonselective beta-blockers are similarly effective in keeping with the hypothesis that changes in portal blood flow are mainly due to the block of beta 1-receptors.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Galactose elimination capacity and liver volume in aging man.

The galactose elimination capacity, a measure of the functional liver cell mass, and liver volume were measured in 50 normal subjects of five different age groups (less than 50, 51 to 60, 61 to 70, 71 to 80 and greater than 81 years). The volume of the liver was evaluated by ultrasonography. All subjects had normal routine liver function tests and no history of liver disease. Galactose elimination progressively decreased from 3.05 +/- 0.58 (S.D.) mmoles per min in younger subjects to 1.83 +/- 0.24 mmoles per min in subjects over 81 (p less than 0.00003), without any change in the apparent volume of distribution of the sugar. Similarly, the estimated volume of the liver decreased from 110 +/- 14 units to 75 +/- 13 units with increasing age (p less than 0.0002). Both galactose elimination capacity and the estimated liver volume inversely correlated with age (r = -0.728 and r = -0.579, respectively) whereas a positive correlation was observed between galactose elimination and the estimated liver volume (r = 0.520). Part correlation analysis confirmed that age, when entered in a multiple regression already containing body weight and estimated liver volume as independent variables, had a significant effect on liver function, whereas no significant independent effect of liver volume was present. Both age and body weight had a significant independent effect on the estimated liver volume. The maximum functional capacity of the liver, measured by galactose elimination, is reduced in the elderly. Although several factors may play a role, our data suggest that aging is associated with a slight decline in the intrinsic metabolic activity of the hepatic parenchyma.

Adult↗
PubMedDate not supplied

Echo-Doppler measurement of splanchnic blood flow in control and cirrhotic subjects.

Blood flow in the splanchnic veins was studied in cirrhotics and matched controls by means of a system that combines a mechanical sector scanner with a pulsed Doppler. The measurements were validated in an in vitro model. Echo-doppler studies could be carried out reproducibly in only approximately two-thirds of cases because of poor echo transmission or incomplete cooperation. Portal blood velocity was significantly reduced in cirrhotics (10.5 +/- 0.6 cm/s versus 16.0 +/- 0.5 in controls; p less than 0.001), but portal blood flow was normal because of enlarged portal caliber. A complete hemodynamic evaluation of the splenic and superior mesenteric veins was possible in only a few subjects. In selected patients the technique may prove relevant in the study of hemodynamic effects of drugs and surgery on portal blood flow.

Adult↗