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E Rocchi

Publications and source records attributed to E Rocchi.

At least 19 recordsLinked to original sources
PubMed2004

Pro-oxidant and antioxidant factors in acute intermittent porphyria: family studies.

Given the crucial role of iron and porphyrins in oxidative cellular damage in the chronic porphyrias, we undertook an extensive study in families with acute porphyrias to evaluate the possible role of similar oxidative damage in these diseases, whose natural history is often also complicated by neoplastic evolution. Four unrelated patients with acute intermittent porphyria (AIP) were studied together with 37 members of four different families. Aminolevulinic acid and porphobilinogen were measured in urine, and porphyrins in urine, plasma and stools. The activity of the congenitally deficient enzyme, porphobilinogen deaminase, and the concentrations of plasma iron, transferrin, ferritin, and various antioxidants (ascorbic acid, retinol, tocopherol, alpha- and beta-carotene, by a personal HPLC method) and the urinary and plasma metabolites of nitrous oxide were also assayed. The results showed no relationship between the observed increase of porphyrin metabolites and the presence of markers of oxidative damage or the decrease of circulating antioxidants: however, when such a decrease was registered, it depended on spontaneous or iatrogenic iron accumulation. We conclude that family screening, recommended for the identification of AIP carriers, must also include evaluation of iron stores with a view to preventing the oxidative damage and in order to forestall the neoplastic evolution of the disease.

Adolescent↗
PubMed2002

Molecular characterization of porphyrias in Italy: a diagnostic flow-chart.

The porphyrias are disorders associated with inherited or acquired enzyme deficiencies in the heme biosynthetic pathway. The differential diagnosis is often difficult since the phenotype is very similar in some forms and the biochemical tests are not commonly available. Here we provide an update on the molecular diagnosis of porphyrias in Italy and a flow-chart to facilitate the identification of mutations in heme biosynthetic genes. The molecular analysis has allowed us to identify the molecular defect underlying the disease in 66 probands with different porphyrias [acute intermittent porphyria (AIP), variegate porphyria (VP), porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP)]. No Italian patients with defects in coproporphyrinogen oxidise (CPOX) gene, responsible for hereditary coproporphyria (HCP), have been detected. The molecular characterization has been extended to 115 relatives with the identification of 55 asymptomatic mutation carriers and 60 normal subjects. We have so far identified 50 different mutations among 4 genes associated with the most common porphyrias showing a high molecular heterogeneity: 22 in the hydroxymethylbilane synthase (HMBS) gene (AIP), 7 in the protoporphyrinogen oxidase (PPOX) gene (VP), 16 in the uroporphyrinogen decarboxylase (UROD) gene (PCT) and 5 in the ferrochelatase (FECH) gene (EPP). Among the 50 molecular defects, 29 seem to be restricted to the Italian population.

DNA↗
PubMed2001

Antioxidant liposoluble vitamins and carotenoids in chronic hepatitis.

Background: It is known that antioxidant liposoluble vitamins and carotenoids are reduced in liver cirrhosis, but little is known about chronic viral hepatitis, where oxidative damage has to be taken into account. Methods: Fifty-five patients with chronic hepatitis, mainly C virus-related, were matched with 16 patients with biliary stones and 20 healthy controls. Plasma and liver analyses were carried out using a well-tried HPLC technique that affords an accurate quantification of retinol, tocopherol, alpha- and beta-carotene, cryptoxanthin, and lycopene. Results: Plasma concentration of retinol, tocopherol, beta-carotene, and lycopene was significantly decreased in both patient groups, particularly in those with chronic hepatitis. In contrast, liver concentration of both esterified and free retinol, tocopherol, and some carotenoids was better preserved in the hepatitis group than in the cholelithiasis group. A strict correspondence between aminotransferases and the amount of liver-stored retinol was documented. Conclusions: Plasma vitamin and carotenoid depletion co-existing with preserved liver storage may indicate a functional defect in liver pool mobilization or even a real depletion of the antioxidant defenses, which play a key role in averting cellular damage. The implications for nutrition and therapy need to be taken into account.

Journal Article↗
PubMed2001

Prognostic features and survival of hepatocellular carcinoma in Italy: impact of stage of disease.

The aim of this study was to evaluate the prognostic factors at presentation and survival in Italian patients with hepatocellular carcinoma (HCC). Clinical and demographic data of 176 patients consecutively observed from 1993 to 1997 were evaluated by univariate and multivariate analyses. Overall median survival was 18 months. At univariate analysis, low albumin, high bilirubin, high alkaline phosphatase, high alpha-fetoprotein (AFP); high platelet count, hepatitis B surface antigen (HBsAg)-positivity, the presence of ascites, of encephalopathy, of portal vein thrombosis (PVT), male sex, no treatment, poor differentiation, untreatable tumours and incidental diagnosis were each associated with shorter survival. HBsAg-positive subjects more often presented with untreatable lesions or diffuse tumours (P=0.001 and P=0.007, respectively) and had significantly worse survival (P=0.0057). By multiple regression analysis, low albumin, high bilirubin, abnormal AFP, presence of PVT and of untreatable lesions were independent risk factors for worse survival. Thus, the most important factors influencing survival are the degree of functional impairment of the liver, the presence of hepatitis B viral (HBV) infection, the type of diagnosis and the aggressiveness of the tumour.

Adult↗
PubMed2000

BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells.

We have previously described a mitoxantrone-resistant MCF7 cell line that is cross-resistant to topotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), and 9-aminocamptothecin, but not to camptothecin. A novel mechanism that resulted in decreased topotecan accumulation in MCF7/MX cells was proposed (Yang et al. Cancer Res 55: 4004-4009, 1995). We now have developed a topotecan-resistant cancer cell line from wild-type MCF7 cells. MCF7/TPT300 cells were 68.9-fold resistant to topotecan, 68.3-fold to 10-hydroxy-7-ethylcamptothecin (SN-38), and 116-fold to mitoxantrone, but only 4.1-fold to camptothecin. Topotecan efflux was increased in MCF7/TPT300 cells compared with MCF7/WT cells, and this increase was reversed upon ATP depletion by sodium azide, suggesting an energy-dependent drug efflux mechanism. However, MCF7/TPT300 cells did not overexpress P-glycoprotein or the multidrug resistance-associated protein (MRP1). In contrast, overexpression of the breast cancer resistance protein (BCRP/MXR/ABCP) was observed in MCF7/TPT300 cells as well as DNA topoisomerase I down-regulation. Our data suggest that enhanced topotecan efflux contributes partly to topotecan resistance in MCF7/TPT300 cells, possibly mediated by BCRP/MXR/ABCP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane.

The products of the ABC gene family can be generally classified as either full-transporters of half-transporters. Full-transporters are expressed in the plasma membrane, whereas half-transporters are usually found in intracellular membranes. Recently, an ABC half-transporter, the ABCG2 gene product Breast Cancer/Mitoxantrone Resistance Protein (BCRP/MXR), has been shown to cause mitoxantrone and topotecan resistance. The purpose of this study was to determine the expression and the intracellular localization of this protein in various drug-resistant cell lines. BCRP/MXR expression was determined by Western blot and immunohistochemistry. This protein is highly overexpressed in several drug-resistant cell lines and localizes predominantly to the plasma membrane, instead of to intracellular membranes as seen with all other known half-transporters. Therefore, BCRP/MXR is unique among the ABC half-transporters by being localized to the plasma membrane.

ATP-Binding Cassette Transporters↗
PubMed2000

Mortality in a population with long-term exposure to inorganic selenium via drinking water.

We analyzed the 1986-1997 mortality in a cohort of 2065 residents of an Italian municipality which had been exposed to drinking water with a high content of inorganic selenium over a long period of time, and compared it with mortality in the remainder of the municipal population. Mortality from malignant neoplasms increased [standardized mortality ratio (SMR) 1.17, 95% confidence interval (CI) 0.96-1.42], mainly due to an excess mortality from melanoma and colorectal cancer in both sexes, kidney cancer in men, and lymphoid malignancies in women. Overall cardiovascular mortality changed little (SMR 1.05, 95% CI 0.89-1.23), despite the higher cerebrovascular mortality (SMR 1.43, 95% CI 1.03-1.93). Coronary disease mortality slightly decreased (SMR 0.87, 95% CI 0.63-1.16), due to a low mortality among women. We also noted an excess mortality from Parkinson's disease in men and from motor neuron disease in women. Evaluation of these findings is, however, hampered by the lack of information about potential lifestyle confounders, the fact that the exposure could only be characterized by a simple dichotomization, and the inconsistencies of most estimates between the two sexes.

Adult↗
PubMed1999

Circulating pro- and antioxidant factors in iron and porphyrin metabolism disorders.

BACKGROUND: Porphyria cutanea tarda and haemochromatosis are taken to be spontaneous human models of oxidative cellular damage, with an increased risk of fibrosis and cancer evolution. AIM: To define the relative pro-oxidant roles of porphyrin and iron, in their different molecular forms, and their effects on antioxidant biological systems. PATIENTS: A group of 17 patients with porphyria cutanea tarda and a group of 14 patients with primary and secondary haemochromatosis, were compared with 21 healthy controls. METHODS: Plasma retinol, tocopherol, alpha- and beta-carotene, ascorbic acid, glutathione, malonyldialdehyde and red blood cell free iron were determined using high performance liquid chromatography. RESULTS: Only a modest increase in iron stores was demonstrated in the porphyria cutanea tarda group; in the haemochromatosis patients ferritin levels were almost seven times higher. By contrast, there was a sharp and virtually identical increase in red blood cell free iron and malonyldialdehyde in both the patient groups. A significant reduction was observed in retinol, alpha-, beta-carotene and red blood cell glutathione levels being more marked in porphyria cutanea tarda than in haemochromatosis patients. CONCLUSIONS: The study confirms the strong pro-oxidant effects of porphyrins in vivo, through an induction of the free toxic iron form, even though the total iron pool is not greatly expanded. The additional free-iron and porphyrin oxidant effects are documented both in red blood cell and plasma in the porphyria cutanea tarda group. It confirmed that aging exerts a negative influence in terms of pro- and antioxidant balance in all cases, but particularly in the haemochromatosis group.

Antioxidants↗
PubMed1997

Hepatic tocopherol content in primary hepatocellular carcinoma and liver metastases.

The high incidence of hepatocellular carcinoma (HCC) in cirrhosis, where previous studies have indicated a severe reduction in several antioxidant vitamin factors, prompted us to compare plasma liposoluble vitamins with tocopherol content in healthy and neoplastic liver tissue in humans. This, with a view to a more positive preventive dietary approach, given the conflicting results obtained by liposoluble vitamin dietary supplementation in different malignancies. Eleven patients with cirrhosis, 18 patients affected by cirrhosis with HCC, and 10 patients with liver metastases (LM) from digestive tract adenocarcinomas were compared with controls who had undergone perlaparoscopic cholecistectomy. Plasma alpha- and beta-carotene, retinol and tocopherol, together with liver tocopherol, from both nonmalignant portions and malignant nodules of the same organ, were determined by high-performance liquid chromatography following a well-assessed technique. The results confirm a trend towards a reduction in circulating carotenoids and tocopherol in cirrhosis and in patients affected by cirrhosis with HCC. Tocopherol content in liver tissue is significantly decreased in cirrhosis (0.26 + 0.03 micromol/g prot., mean + SEM, P < .001) and in cirrhotic areas of the HCC group (0.31 + 0.02, P < .002), with respect to its content in liver specimens of healthy controls (0.46 + 0.03) and in healthy areas of the same organ in patients with LM (0.41 + 0.03). Tocopherol concentration is further reduced by 50% in malignant liver nodules of HCC, with respect to surrounding cirrhotic tissue, whereas in metastatic liver nodules from digestive neoplasms the tocopherol content is almost twice that of healthy surrounding areas. This unpredictable tocopherol behavior in liver specimens, of secondary as opposed to primary malignancies of the liver, affords further insight into the conflicting effects of liposoluble vitamins employed in the chemopreventive treatment of different malignant diseases, where hepatic tocopherol concentration show opposite trends: halved in primary HCC and doubled in LM of digestive adenocarcinomas, with respect to healthy controls.

Aged↗
PubMed1996

Multi-frequency bioelectric impedance measurements for predicting body water compartments in patients with non-ascitic liver cirrhosis.

We assessed total body water (TBW) and extracellular water (ECW) in thirty-four non-ascitic cirrhotics and twenty healthy controls by 2H2O and Br dilution. In the same subjects, bioelectric impedance (BI) was recorded at multiple frequencies. Body hydration was similar for controls (mean 55.6 (SD 6.7)), less-severe cirrhotics (Child-Pugh classification A; CPA; n 21, mean 56.2 (SD 6.2)) and moderately-severe cirrhotics (Child-Pugh classification B; CPB; n 13, mean 57.2 (SD 5.4)). However, intracellular water standardized per litre TBW was significantly higher in CPB subjects (mean 27.0 (SD 7.5); P < 0.01) compared with CPA (mean 21.3 (SD 10.6)) and control subjects (mean 18.0 (SD 9.8)). Published formulas for predicting TBW and ECW from BI at multiple frequencies were applied to the cirrhotics. These formulas gave accurate predictions of TBW and ECW, although standard errors of estimates were higher for CPB subjects (TBW < or = 2.5 and ECW < or = 2.1 l) than those for CPA (TBW < or = 2.0 and ECW < or = 1.8 l) and control (TBW 1.4 and ECW 0.9 l) subjects.

Body Water↗
PubMed1995

Thyroid hormone promotes BCL-2 expression and prevents apoptosis of early differentiating cerebellar granule neurons.

Programmed cell death is a basic cellular process that has aroused much interest in recent years. Like immune cells, cultures of cerebellar granule neurons are very homogeneous and provide a unique opportunity for quantifying by flow cytometry one form of programmed cell death in the CNS, the apoptosis, and for studying its regulation by neurotrophic factors. We found that thyroid hormone promoted postmitotic survival by preventing the apoptosis of newly formed and early differentiated granule neurons in a dose-dependent manner. This regulation could be through the protein bcl-2, which is known to prevent cell death. This protein was present at all stages of granule neuron differentiation and appeared to be developmentally regulated. It was underexpressed in apoptotic granule neurons. The protein content of the cerebellum in hypothyroid rats was drastically reduced. In contrast, thyroid hormone caused a marked dose-dependent increase in the amounts of this protein in granule neuron cultures. The possibility that thyroid hormone may be directly or indirectly required to promote cell survival is discussed, in terms of the hormone control of the local delivery of neurotrophins, such as NGF and NT-3, as well as the expression of their low affinity receptors, gp75. We suggest that thyroid hormone has a permissive action on the developing CNS.

Animals↗
PubMed1995

Liposoluble vitamins and naturally occurring carotenoids in porphyria cutanea tarda.

The authors consider two groups of patients with overt sporadic porphyria cutanea tarda (PCT) from different continents, with the aim of evaluating the possible impairment of the liposoluble antioxidative system, given the possible synergic effect of porphyrins and iron in promoting oxidative cellular damage. Twenty-three Italian outpatients with overt sporadic PCT and 11 outpatients with PCT from Buenos Aires (Argentina) were matched with 60 patients with liver cirrhosis and 52 healthy Italian controls. Serum levels of alpha- and beta-carotene, cryptoxanthin, zeaxanthin, lutein, lycopene, retinol and alpha-tocopherol were detected by a high-performance liquid chromatographic technique devised in our laboratory, which afforded an accurate and simultaneous resolution of all these compounds. The results point to a significant reduction in plasma levels of alpha- and beta-carotene in both the PCT populations with respect not only to controls, but also to the cirrhotic population, which had more severe liver damage. Moreover, other carotenoids with proven antioxidative properties, like cryptoxanthin and lycopene, are greatly reduced in our PCT populations. This confirms the suggested synergic effect of iron and porphyrins in the oxidative intracellular damage with consequent depletion of antioxidative liposoluble molecules.

Alkaline Phosphatase↗
PubMed1994

Zinc and magnesium in liver cirrhosis.

The Authors determined zinc (Zn) and magnesium (Mg) in the plasma, urine, erythrocytes (RBCs), mono- and polymorphonuclear cells (MNCs and PMNs) of patients with overt alcoholic and non-alcoholic liver cirrhosis. In order to obtain a clearer clinical picture, biochemical and nutritional parameters (retinol, tocopherol, six different carotenoids, creatinine-height index and tricipital skinfold), as well as markers of portal hypertension (spleno-portal size and platelet count) were also evaluated. The plasma levels of Zn and Mg were found to be reduced, as were the urine levels of Mg. Urine Zn, on the other hand, was higher than normal. Plasma Zn correlated inversely, and urine Zn directly, with the severity of the disease, rather than with alcohol consumption or treatment with diuretics. Protein metabolism impairment would appear to affect the plasma transport of Zn rather than its overall availability in the organism; the opposite was found in the case of Mg, the availability of which appeared to be reduced. Determination of the two elements in RBCs, MNCs and PMNs suggested that a true nutritional deficit cannot be demonstrated. MNCs, rather than RBCs or PMNs seem better to reflect tissue status of trace elements.

Erythrocytes↗
PubMed1994

[Magnetic resonance and hepatic siderosis].

The principles of generation of magnetic resonance imaging (MRI) are resumed by briefly explaining the effects of an external magnetic field (EMF) on hydrogen nuclei and of pulses of radiofrequency (RF) radiation. The latter creates a resonant effect, and the same nuclei, moved from the external field axis, when RF pulse is stopped, will "relax" to their original alignment in the magnetic field and in so doing radiate the absorbed energy to their surroundings. This energy provides a signal that can be detected and spatially resolved by the receiver coil wrapped around the patient, through a computerized system. After briefly explaining also the distinctive parameters T2 and T1, the author presents his experience in the MRI detection of different degrees of siderosis of the liver--ranging from idiopathic and secondary haemochromatosis to milder siderosis of alcoholic liver disease and porphyria cutanea tarda. The results were accomplished by employing an equipment operating at an enhanced field strength (1.5 Tesla). Previous reports have validated this technique in order to distinguish idiopathic from secondary haemochromatosis. Furthermore, the present study shows that even low to moderate degrees of liver iron deposition can be appreciated and roughly quantitated by the decrease of the transverse relaxation time (T2), which resulted proportional to the amount of liver iron, under these operating conditions. Thus, MRI is proposed as an useful and non-invasive way to detect iron deposition and to follow up iron depletion treatments.

Hemochromatosis↗
PubMed1993

Magnetic resonance imaging and different levels of iron overload in chronic liver disease.

The need for accurate and noninvasive evaluation of liver iron stores prompted us to evaluate the reliability of high-field magnetic resonance imaging equipment in liver patients with low or moderate siderosis, given the poor results obtained using systems operating at low field strength in such cases. Twenty patients with sporadic porphyria cutanea tarda and 28 with comparable chronic liver diseases (chronic hepatitis or cirrhosis) and moderate siderosis were compared with 10 patients with idiopathic or secondary hemochromatosis and 10 healthy controls. Plasma iron profile, ferritin concentration and liver iron concentration, determined with atomic absorption spectroscopy, were matched with the magnetic resonance parameters-namely, transverse relaxation time and the signal intensity for a given proton amount, obtained with equipment operating at a field strength of 1.5 T. Hemochromatosis patients with mean liver iron concentrations of 550 mumol/gm dry wt (vs. 10 mumol of controls) exhibited an impressive reduction in the signal intensity with respect to the other three groups, and this reduction prevented any further comparison with the same porphyria cutanea tarda and chronic liver disease groups, whose liver iron level was twice that of the controls. The signal intensity remained almost unchanged in the latter groups, whereas the transverse relaxation time was significantly reduced. Moreover, correlation with liver iron was significantly inverse in the case of the transverse relaxation time (n = 17, r = 0.62, p = 0.008) and direct in the case of the transverse relaxation rate. The transverse relaxation time values returned to normal in five patients who had completed an iron-depletion program.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Nutrition and malnutrition in hepatic cirrhosis].

Liver cirrhosis is associated with malnutrition in 10 to 90% of cases, following different authors. This prompted us to compare our previous studies with recent literature data in order to review this topic from a practical standpoint. Several pathophysiological factors are blamed for this state and mainly protein and lipid-restricted diets from among these. Some lean and fat body mass indices predictive of malnutrition are proposed taking into account the influence of liver disease in their evaluation. Nitrogen balance derangements and liposoluble vitamins and carotenoids plasma decrease are highlighted as sensitive nutritional parameters. After a brief review of amino acid, glucose and lipid metabolic derangements, some nutritional guidelines are provided by distinguishing oral selective supports from the parenteral nutrition. The latter, being reserved to moderate-severe encephalopathy or to hemorrhagic conditions, is proposed following an algorithm which takes into account different nutritional principles as a function of the severity of the clinical condition. During the first period (24-48 hrs) parenteral fluids, electrolytes, dextrose and whole blood or derivatives (when necessary) are provided; lactulose or lactitol via nasogastric tube, or by enema, are started as well. During the following 48-72 hrs branched-chain amino acids alone or enriched solutions are added taking into account an optimum calorie/nitrogen ratio. Finally, vegetable lipids, vitamins and oligoelements can be added if intravenous nutrition must be maintained, with a view of warranting the most complete nutritional approach to these severely malnourished patients.

Dietary Carbohydrates↗
PubMed1992

Regulation of transferrin, transferrin receptor, and ferritin genes in human duodenum.

To gain insights at the molecular level into the expression of iron-regulated genes [transferrin (Tf), transferrin receptor (TfR), and ferritin H and L subunits] in human intestinal areas relevant to iron absorption, the steady-state levels of specific messenger RNAs (mRNAs) were analyzed in gastric and duodenal samples obtained from 6 normal subjects, or 10 patients with anemia, 14 patients with untreated iron overload, and 8 patients with various gastrointestinal disorders. No Tf mRNA was detected in human gastroduodenal tissue, confirming earlier findings in the rat. In normal subjects, although higher levels of ferritin H- and L-subunit mRNAs were consistently found in duodenal than in gastric samples, no differences in the content of TfR transcripts were detected. However, a dramatic increase in TfR mRNA levels was specifically found in duodenal samples from subjects with mild iron deficiency but severe anemia. This response of the TfR gene is presumably secondary to decreased cellular iron content due to its accelerated transfer into the bloodstream, as also indicated by the low levels of ferritin subunit mRNAs found in the same tissue samples, and is not linked to faster growth rate of mucosal cells because no changes in duodenal expression of histone, a growth-related gene, were detected. In patients with secondary iron overload, a down-regulation of duodenal TfR gene expression and a concomitant increase in ferritin mRNA content were documented. On the contrary, a lack of TfR gene down-regulation and an abnormally low accumulation of ferritin H- and L-subunit mRNAs were detected in the duodenums of subjects with idiopathic hemochromatosis. Whether these molecular abnormalities in idiopathic hemochromatosis are relevant to the metabolic defect(s) of the disease is presently unknown.

Adult↗