Search PubMed⌕ Search

Biomedical subjects

A Romanelli

Publications and source records attributed to A Romanelli.

At least 37 records · Page 2Linked to original sources
PubMed1997

Dexfenfluramine modulates hepatic glycogen metabolism by a calcium-dependent pathway.

In this study, the mechanism of action of dexfenfluramine (DEXF) at the hepatic level was investigated. The drug is shown to bind to the alpha 1-adrenergic receptor and to increase intracellular calcium in isolated rat hepatocytes, thereby activating phosphorylase via a calcium-dependent mechanism. Moreover, phosphorylase activation by DEXF was inhibited by different agents that interfere with the alpha 1-adrenergic signalling system: prazosin, phorbol 12 alpha-myristate 13 beta-acetate (PMA), and DEXF itself. We also show that phosphorylase activation induced by catecholamines and analogues (epinephrine, phenylephrine), whose actions are mediated by a calcium-dependent mechanism, was counteracted by the drug in the submillimolar range (0.1-1 mM). The activation of glycogenolysis by the drug is accompanied by a stimulation of the glycolytic flux (54% increase in lactate plus pyruvate accumulation), consistent with an increase in fructose-2,6-bisphosphate (F-2,6-BP) levels (36%). These results indicate that the interaction of DEXF with the alpha 1-adrenergic receptor channels glucose 6-phosphate derived from glycogen away from glucose production into the glycolytic pathway.

Adrenergic Agonists↗
PubMed1996

Cisplatin-associated anaemia in patients with solid tumours. A retrospective evaluation and considerations relative to erythropoietin administration.

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatin-containing regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.

Anemia↗
PubMed1995

Modulation of glucagon-induced glucose production by dexfenfluramine in rat hepatocytes.

The mechanism of the antihyperglycaemic action of dexfenfluramine (DEXF) was investigated in isolated rat hepatocytes exposed to glucagon. Preincubation of hepatocytes with DEXF caused a dose-dependent inhibition of cyclic AMP formation by 100 nM glucagon (Ki = 0.29 mM) that was almost complete at 1 mM DEXF. Surprisingly, glucagon-induced phosphorylase activation was not affected by DEXF despite the significant drop in cyclic AMP levels. Glucose production stimulated by glucagon was inhibited by up to 48% by 1 mM DEXF, and the rate of glucose production correlated positively with the steady-state concentration of glucose 6-phosphate. DEXF also partially restored lactate + pyruvate production which was abolished by an optimal concentration of glucagon. Although DEXF was not able to prevent the inactivation of pyruvate kinase by glucagon, the lack of further accumulation of phosphoenolpyruvate in DEXF-treated cells supports the conclusion that the flux through pyruvate kinase is stimulated, probably via the increase in fructose 2,6-bisphosphate, thereby increasing glycolysis. Our results thus indicate that DEXF counteracts the inhibition of glycolysis by glucagon and that this property might contribute to the antihyperglycaemic effect of this drug. Furthermore, this study shows that, in the presence of the drug, glucagon caused phosphorylase activation and pyruvate kinase inactivation without a significant increase in cyclic AMP levels.

Animals↗
PubMed1994

Absence of glucose uptake by liver microsomes: an explanation for the complete latency of glucose dehydrogenase.

The permeability of rat liver microsomes to glucose was investigated in relation to the hexose-6-phosphate dehydrogenase system (EC 1.1.1.47). It was found that glucose-6-phosphate dehydrogenase activity could be assayed with NADP as coenzyme in both untreated and detergent-treated microsomes. However, when glucose was used as substrate, activity was only measurable in detergent-treated microsomes. Moreover, radioactive glucose added to microsomes in a variety of experimental conditions was never taken up by the vesicles. Our results indicate that NADP (or NAD) availability is probably not the reason for the absence of glucose dehydrogenase activity in untreated microsomes but rather membrane impermeability to glucose would account for the complete latency observed. This finding calls for a reevaluation of glucose transport in relation to other enzymes of the endoplasmic reticulum, such as glucose-6-phosphatase.

Animals↗
PubMed1994

Stages I and II non-Hodgkin's lymphoma of the gastrointestinal tract. Retrospective analysis of 79 patients and review of the literature.

We reviewed the medical records of 79 patients with primary gastrointestinal lymphoma (GI-NHL), defined according to the criteria of Dawson et al. (without involvement of liver, spleen, peripheral or mediastinal lymph nodes, or bone marrow), observed and treated in our institution between 1973-90. The most common disease site was the stomach (70 patients), followed by the small bowel (five patients) and the large bowel (four patients). The stage was IE in 36 cases and IIE in 43. Radical surgery or surgical debulking was the main therapeutic approach (67 patients); 12 patients received only chemotherapy, eight of whom had tumors considered unresectable at laparotomy. After surgery, most of the patients received chemotherapy; radiotherapy (RT) was given to only four patients. Surgically calculated overall survival (OS) rates at 5 years for the patients treated with surgery plus chemotherapy were 64% (radical surgery) and 46% (surgical debulking with microscopic lymphoma residue). For the 12 patients treated with chemotherapy alone, OS at 5 years was 0%. Our findings, in accordance with most published data, suggest that surgery, together with stage and tumor size, remains an important prognostic factor of survival in primary GI-NHL, especially when it is radical. In patients with negative prognostic factors (bulky disease, high-grade histologic type, microscopic residue, and stage II), postoperative chemotherapy and RT decrease the risk of distant failure and local recurrence.

Adult↗
PubMed1993

Hot occupation and nephrolithiasis.

We investigated the prevalence of stone disease and urinary stone risk factors in machinists chronically exposed to a hot environment and massive sweating, without interference of nephrotoxic metals or other lithogenic compounds. The study was performed at a glass plant and exposure to heat stress was estimated by the Wet Bulb Globe Temperature climatic index. The prevalence of nephrolithiasis on the entire population of the machinists was 8.5% (20 of 236), while the prevalence on the controls working in normal temperature was 2.4% (4 of 165) (p = 0.03). A high incidence (38.8%) of uric acid stones was present in the workers exposed to heat stress. Among the urinary stone risk indexes determined for 3 days during the 8-hour work shift on a randomly selected sample of 21 workers exposed and 21 workers not exposed to heat stress without any evidence of stone disease significant differences were found in uric acid concentration (722 +/- 195 versus 482 +/- 184 mg./l., p < 0.001), specific gravity (1,026 +/- 4 versus 1,021 +/- 6, p < 0.005) and pH (5.31 +/- 0.28 versus 5.64 +/- 0.54, p < 0.02), respectively. Thus, high uric acid relative supersaturation was present during occupation in hot temperatures (8.67 +/- 3.49) compared to occupation in normal temperatures (4.15 +/- 2.7) (p < 0.001). This study confirms that chronic dehydration represents a real lithogenic risk factor, mainly for uric acid stones, and adequate fluid intake is recommended during hot occupations.

Adult↗
PubMed1993

A prevalence study of carotid atherosclerotic disease in patients aged above 60.

The results of Doppler sonography and the echotomographic evaluation of extracranial arteries performed on 139 asymptomatic patients aged above 60 are presented. Atheromatous lesions were found in 54 (38.85%) of the subjects, though most had no hemodynamic effects. Statistical analysis showed an increase in both number and gravity of lesions with advancing age in females alone. No significant association was found between risk factors and atheromatous lesions, except for smoking in males.

Age Factors↗
PubMed1993

[The epidemiology of cardiovascular malformations. III. The prevalence and follow-up of 46,895 live births at the Careggi Maternity Hospital, Florence, in 1975-1984].

BACKGROUND: To evaluate the prevalence of congenital heart disease in a homogeneous population we examined 46,895 liveborns in the period from January 1975 to December 1984 in the Careggi Maternity Hospital in Florence. METHODS: The diagnosis of congenital heart disease was made in 579 newborns within five days from birth. All newborns were examined clinically by two neonatologists and referred to the pediatric cardiologist in case of cardiac abnormalities. An ECG was recorded in each of them, chest x-ray in 87% and echo in those who were born after 1980. The children were followed up until December 1989. Mean follow-up period was 6 years. RESULTS: The annual incidence ranged from 9.5% to 15.7% (average 12.3%). Chromosomic anomalies and extra-cardiac malformations occurred in 102 children (17.6%), respectively in 50 (8.6%) and 52 (9.0%) cases. Ventricular septal defect (VSD) and the patent ductus arteriosus (PDA), isolated or associated, were the most frequently recognized congenital heart diseases. 52 children (9.0%) were lost at follow-up. The initial diagnosis was changed in 11/579 cases. In 187 children (32.3%) there was a spontaneous disappearance of clinical and/or instrumental findings that had suggested the presence of congenital heart disease at birth: in 144 the diagnosis was VSD, and in 43 PDA. The prevalence of VSD was 4.7 per thousand in the period 1975-80 and 8.6 in the period 1981-84. 131 children (22.6%) died, 127 (96.9%) of them in the first year of life. 52 children were operated on and pulmonary valvuloplasty was performed in 5. CONCLUSIONS: The prevalence of congenital heart disease does not change during a long observation period, while the number of VSDs increases. VSD and PDA spontaneously close in a high percentage of cases. The study suggests the usefulness of an intensive care unit for newborns with severe congenital heart disease, especially for those in the first year of life.

Abnormalities, Multiple↗
PubMed1988

Brain dopamine as a target for solvent toxicity: effects of some monocyclic aromatic hydrocarbons.

Adult male rabbits were exposed to toluene, xylene, styrene, ethylbenzene, vinyltoluene or were dosed with hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tubero-infundibular dopamine. Such an effect was also caused by treatment with mandelic and phenylglyoxylic acids. These results indicate that dopamine is a target for some solvents of their metabolites, the presence of a lateral vinyl- or ethyl-chain which may be biotransformed into alpha-keto acids being crucial for the effect. Experiments in vitro suggest that dopamine condenses non-enzymatically with reactive carbonylic groups of such and other alpha-keto acids, thus becoming ineffective as neurotransmitter. This mechanism might account for the neurobehavioral and neuroendocrine changes which have been reported in workers occupationally exposed to styrene and to some solvent mixtures.

Animals↗
PubMed1987

Adrenal response in the pathogenesis of arterial hypertension in workers exposed to high noise levels.

Some neuroendocrine parameters known as stress indices were examined in two groups of healthy male workers in a glass factory: the first group (60 subjects) was exposed to high environmental noise levels [greater than 90 dB(A)]; the second group (52 subjects) was exposed to low noise levels [less than 78 dB(A)]. Subjects with histories of cardiovascular diseases or high arterial pressure were excluded from the study. In both groups serum catecholamines and cortisol, and urinary vanilmandelic and homovanillic acids were evaluated at the beginning and middle of morning and afternoon work-shifts, by high performance liquid chromatography with electrochemical detection. Norepinephrine, epinephrine and vanilmandelic acid were significantly increased (P less than 0.01) during work-shifts in the group exposed to 90 dB(A), compared with baseline levels and also with catecholamine levels in the group exposed to 78 dB(A). Serum dopamine, cortisol and homovanillic acid showed no significant differences. The increased stimulation of the sympatho-adrenal system in response to high and prolonged noise exposure might lead to an abnormal response of the cardiovascular system with increasing arterial pressure values.

Adrenal Glands↗
PubMed1986

Effects of some monocyclic aromatic solvents and their metabolites on brain dopamine in rabbits.

Adult male rabbits were exposed to high concentrations (750 ppm, 12 hours daily for 7 days) of toluene, xylenes, styrene, ethylbenzene, vinyltoluene (3-methylstyrene), and 7-methyl-styrene vapours or were dosed with 4 mM/kg/day i.p. of hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tuberoinfundibular dopamine. Such an effect was also caused by treatment with phenylglyoxylic and mandelic acids. Dopamine depletion was associated with an increase in homovanillic acid concentration in the same regions. These results indicate that dopamine metabolism is a target for the neurotoxic effects of some monocyclic aromatic hydrocarbons and their metabolites, a lateral vinyl- or ethyl-chain being crucial for the structure/activity relationship of such compounds.

Animals↗
PubMed1985

Styrene metabolism and striatal dopamine depletion in rabbits.

The striatal concentration of dopamine (DA), norepinephrine (NE), and homovanillic acid (HVA) was assessed in adult male rabbits exposed to styrene vapours or dosed with mandelic acid (MA), phenylglyoxylic acid (PGA) and phenylglycine (PG). Styrene exposure produced a marked and dose-dependent decrease in striatal DA, concomitant with a consistent increase in HVA. The same effects were caused by i.p. administration of PGA and PG, but not of MA. The increased catabolism of DA was concomitant with a normal turnover time after inhibition of tyrosine hydroxylase by the administration of methyl-p-tyrosine. The amination of PGA to PG with a subsequent competition of the latter with DA for the vesicular storage capacity is suggested as the possible mechanism for styrene-induced brain dysfunction.

Animals↗
PubMed1984

Regional alterations of brain catecholamines by styrene exposure in rabbits.

The regional distribution of dopamine, norepinephrine and homovanillic acid was assessed in adult male rabbits exposed to styrene vapours. The turnover of dopamine and norepinephrine was also measured in several brain regions by the decay in endogenous catecholamines after inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine. Styrene exposure produced a marked and dose-dependent decrease in striatal and tuberoinfundibular dopamine, associated with a consistent increase in homovanillic acid content in the same regions. Norepinephrine levels were unaffected by styrene exposure. The observed increase in catabolism of dopamine cannot be explained by the turnover time, which was not significantly different in the exposed as compared to the control rabbits. Competition of a styrene metabolite with dopamine for the vesicular storage capacity or a selective destruction of dopaminergic terminals are suggested as the possible mechanisms for styrene neurotoxicity.

Animals↗