Early biochemical evidence of neoplasm in a case of ascites of unknown origin.
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Biomedical subjects
Publications and source records attributed to C Loguercio.
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Fosinopril is distinguished from other ACE inhibitors by a pharmacokinetic pecularity in the sense that is can be metabolized either by liver or kidney. This was the rationale of the present research the aim of which was to verify if administered to patients with liver cirrhosis the drug was liable to alter global liver function and ability to metabolize drugs. Eight cirrhotic males, mean age 56 years, also suffering from high blood pressure, were studied. In these patients, liver and kidney function tests (BUN, creatinine blood level, serum and urinary electrolytes, creatinine clearance, calcium and phosphor blood level, transaminases, alkaline phosphatase prothrombin time, cholinesterase, gamma-glutamyl-transpeptidase) were carried out at baseline and after 30 days' fosinopril treatment (1 capsule every morning in the fasting state); in addition total functioning liver mass was assessed by the galactose test, and drug-metabolizing capacity by the antipyrine test. Treatment resulted in a significant improvement of pressure values in all patients (p < 0.01) and did not alter liver and kidney function parameters. Besides, no side effects were registered, especially no case of orthostatic hypotension. The antipyrine test was not influenced by fosinopril treatment. Therefore, short-term treatment with this ACE-inhibitor can be concluded to be effective and not to cause additional alterations of liver function in patients with liver cirrhosis.
We measured glutathione and cysteine concentrations in erythrocytes of chronic alcohol misusers with (20 subjects) and without liver cirrhosis (20 subjects). Glutathione levels were decreased, whereas those of cysteine were increased in all patients. Parenteral treatment with S-adenosylmethionine (SAME); (2 g daily in 250 ml 0.15 M NaCl for 15 days) corrected the erythrocyte thiol alterations. We conclude that parenteral treatment with SAME affects the metabolism of SH compounds in erythrocytes of alcoholic patients.
The aim of the study was to evaluate: a) the influence of the diagnosis of liver cirrhosis on the alimentary behaviour of cirrhotic patients; b) the compliance and the effect during observation-time of a personalized diet; c) the modifications, induced by the diet, of some clinical and biochemical parameters, specifically of these correlated to hepatic encephalopathy in 20 non-alcoholic cirrhotic patients. They were entered the study, in stage A-B of liver disease, according to Child-Pugh criteria. No patients received a previous specific dietetic prescription. After the collection of the alimentary intake before and after the diagnosis of liver disease, we prescribed normoprotein and hyposodium diets, reducing or increasing the caloric intake for the patients who were not at their ideal weight. From our study it stands out that the diagnosis induced all patients to reduce their caloric intake, especially of lipids. The appropriate dietetic prescription followed by short run controls led to a general improvement of the evaluated parameters, which was not kept during the following months; as a matter of fact, at the long run control all patients tended to return to their previous alimentary habits, neglecting, in the course of time, the diets they had been prescribed. We can, consequently, maintain that the cirrhotic needs a steady clinical and dietetic control since he seems to undervalue the prescribed therapies.
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Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after ethanol administration with and without pretreatment with parenteral glutathione. Glutathione significantly decreased the extent of ethanol induced macroscopic injury to the mucosa of the gastric body and antrum. Glutathione's protective effect is associated with appreciable inhibition of ethanol induced depletion of gastric sulfhydryl compounds. This is the first report of protection against ethanol induced gastric mucosal damage by a sulfhydryl containing agent in humans.
The work was designed to study the effects of a meat meal on glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma concentrations of glucagon, insulin, growth hormone, renin, aldosterone, total amino acids, and NH3 in healthy humans (H) as well as in patients with Child A liver cirrhosis (LC). The meat meal produced renal hyperaemia and hyperfiltration without changes in the filtration fraction. Fractional Na excretion in urine increased significantly after the meat meal only in LC. Hyperinsulinaemia and hyperglucagonaemia were seen at baseline in LC and were not affected by the meat meal, whereas in H glucagon concentration increased significantly over baseline within 30 min from the meat meal and insulin within 60 min. Growth hormone concentration was normal at baseline in LC and increased significantly 120-180 min after the meal, whereas it was not affected in H. Renin and aldosterone were stable in both H and LC. Plasma amino acid concentration began to increase 60 min after the meat meal, when hyperfiltration was present. The data indicate that in human Child A cirrhosis of the liver renal haemodynamic response to a meat meal is independent of changes in glucagon.
Glutathione (GSH) and cysteine were determined in the plasma and the erythrocytes of alcoholic and non-alcoholic cirrhotics as fluorescent monobromobimane derivatives by high-performance liquid chromatography (HPLC). Cirrhotic patients displayed a significant decrease of plasma GSH, as well as of plasma cysteine, that was related to the degree of liver disease but not to the nutritional conditions. On the contrary, erythrocyte cysteine was found to increase significantly in all cirrhotics, particularly in alcoholics, regardless of the severity of disease. In an attempt to find a possible explanation of these alterations, the GSH synthesizing enzymes, gamma-glutamylcysteine synthetase (GC-s) and GSH synthetase (GSH-s) activities were determined in the erythrocytes. GSH-s activity was significantly lower in cirrhotic patients, whereas GC-s activity did not differ in the three groups.
The intravenous administration of fructose in healthy subjects may induce an increase of blood uric acid and the urinary excretion of urate and xanthine as a result of hepatic adenosine triphosphate (ATP) breakdown. These changes are partially reversed by ATP resynthesis. We studied the effect of fructose load (0.5 g/kg body weight) on the products of ATP metabolism, and the interference of fructose on the galactose test in 10 patients with well compensated cirrhosis compared with 10 healthy controls. The fructose and the fructose/galactose loads induced a significantly greater increase of plasma uric acid in cirrhotics than in controls, with a 60 minute peak in the cirrhotics. Urinary excretion of urate and xanthines was significantly increased (p less than 0.001) only in the cirrhotics after the fructose/galactose load. As expected, the galactose elimination capacity (GEC) calculated with the galactose test, was lower in these patients than in controls. Fructose infusion before galactose did not significantly modify the GEC in either of the two groups compared. The higher uric acid increase induced by fructose in the blood of cirrhotic patients seems to be a good marker of the energy crisis of the diseased liver whereby it is unable to efficiently resynthesize ATP from its breakdown products.
Previous works have documented that pentagastrin has a stimulatory effect on salivary secretion. In this paper, we have studied the action of caerulein, a peptide that has an active gastrin-like terminal tetrapeptide, on salivary secretion in man. Our data documented that caerulein and pentagastrin have similar excitatory effect on gastric secretion in man, but different actions on salivary flow. Caerulein, at increasing doses, inhibits salivary flow, but not the secretion of amylase; this effect is statistically significant at 0.5 micrograms/kg/h which is the same dose that maximally stimulates gastric secretion. The inhibitory effect of caerulein was not reversed by previous injection of papaverin.
This study evaluated the regional distribution of sulfhydryl compounds in the human gastric mucosa and the effect of ethanol on gastric sulfhydryl tissue levels. Total sulfhydryl, glutathione, and cysteine and their oxidized forms were measured in biopsy specimens taken from the gastric body and antrum of 22 healthy volunteers. Total sulfhydryl and glutathione contents of the body of the stomach were significantly higher than those of the antrum. In contrast, cysteine concentration was higher in the gastric antrum than in the body. No difference was found in the levels of oxidized sulfhydryls between the gastric body and antrum. The effect of acute administration of ethanol on gastric sulfhydryl content was studied in nine subjects. Ethanol caused gross mucosal damage and lowered the concentration of sulfhydryl compounds in both the body and the antrum. In 10 chronic alcoholics total sulfhydryl and glutathione, but not cysteine, were markedly decreased in the gastric body but not in the antrum as compared with nonalcoholic controls. In conclusion, 1) the human gastric body contains significantly higher tissue levels of total sulfhydryls and glutathione and lower concentrations of cysteine than the antrum; 2) ethanol in a damaging concentration significantly decreases gastric tissue levels of sulfhydryl compounds; and 3) chronic ethanol intake lowers total sulfhydryl and glutathione tissue levels in the gastric body.
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1. The effects of methanethiol (MT), DL-dithiothreitol (DTT) and N-ethyl-maleimide (NEM) were studied on the electrical activities of the frog cord. 2. Methanethiol depressed spontaneous dorsal and ventral root potentials, whereas no effects were observed on evoked responses. 3. N-ethyl-maleimide, a SH modifying agent, irreversibly depressed electrical cord activities. 4. DL-Dithiothreitol, a SH reducing agent, dramatically increased spontaneous electrical cord pattern. 5. It is suggested that interneuronal membrane sulphydryl groups of dorsal horn cell population are involved in the origin of spontaneous electrical cord activities and that MT interacts with these interneurones, probably oxidizing membrane SH groups.
To evaluate the effect of cerulein on salivary secretion in man, 25 healthy volunteers have been studied. In the morning, before breakfast, saline solution (125 ml/h) has been infused at a constant flow, for one hour. Saline solution has been followed, for other 60', by saline solution + Cerulein at doses of 0.05, 0.1, 0.2, 0.3, 0.5 microgram/Kg/h. These different doses have been administered in different days according to a randomized order. A wash out by saline solution, at same velocity as before, has been carried out after Cerulein . Samples of saliva were collected every 15'. On salivary specimens the amylase activity (U/l) has been dosed. Each dose of Cerulein induced a reduction of salivary flow. By blocking the administration of Cerulein the salivary secretion returned to basal value in about one hour. No inhibitory effect has been noted on amylase secretion using different doses of Cerulein .
The content of plasma thiols was determined in 42 patients with non-alcoholic cirrhosis. Total thiols were evaluated by Ellman's method, glutathione and cysteine by HPLC in fluorescence. Cirrhotic patients showed a significant decrease in plasma thiol content with respect to a control group of 32 healthy subjects, as total sulphydryls as well as glutathione and cysteine. The thiol decrease does not seem to be related to nutritional status or dietetic factors. Our data indicate that liver cirrhosis, independently from alcohol abuse, produces a decrease in all plasma thiols, probably secondary to a complex alteration of the transsulfuration pathway.
This study was undertaken to evaluate by anthropmetric measurements the nutritional status of cirrhotic patients at different stages of the disease and to establish intra- and inter-observer variability in the determination of these parameters. In 60 healthy controls and 108 cirrhotics (63 'well compensated' and 45 'decompensated' groups A and B + C on the Child-Pugh classification respectively) two independent experienced observers measured biceps, triceps, subscapular and overiliac skinfold thicknesses and arm circumference three times. Each observer was unaware of the results obtained by the other. No significant intra- or inter-observer variability was found. The study indicates that skinfold thickness measurements are a reliable and reproducible method of assessing the nutritional status of cirrhotics. It was found that more than 50 per cent of the decompensated patients were malnourished, with skinfold values significantly lower than those of the controls. In comparison with skinfold thickness and arm circumference, parameters such as body weight and lean body mass are unreliable, and other indices such as muscle and/or fat arm area do not add any significant information to the evaluation of the nutritional status of cirrhotics.
Intravenous infusion of pentagastrin increases salivary secretion progressively at doses from 1 to 4 micrograms/kg body weight/h. Pentagastrin also stimulates salivary secretion of amylase. Simultaneous administration of somatostatin, at the dose that inhibits gastric secretion of pentagastrin-stimulated HCl, blocks the effect of pentagastrin on salivary flow, while it does not reduce the amylase concentration. The data suggest that different mechanisms underlie the effects exerted by pentagastrin on salivary flow and on the concentration of amylase in saliva.
Autonomic diabetic neuropathy of the alimentary canal takes several basic forms: a) oesophagopathy , b) gastroparesis, c) enteropathy, d) bile duct disorders. In many cases three are no subjective symptoms. In other the onset of the clinical condition may take acute and dangerous forms as in gastropathy. In still other cases e.g. enteropathy, the neuropathy may develop in bizarre and unexpected ways which are highly damaging to the patient's quality of life though in most cases they are not fatal. Bile disorders involving minimal motility after stimulus, as in denervation and reduced sensitivity to pain are particularly significant. Diabetics are more likely to suffer from calculosis (59.6% of cases), with septic complications (20% in diabetics compared to 7.8% in non-diabetics) or cholestasis (20% in diabetics v. 15.8% in non-diabetics). These figures indicate that all diabetics and especially the elderly should be subjected to careful examination to identify any bile disorders.