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Biomedical subjects

B Daniele

Publications and source records attributed to B Daniele.

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

Oestradiol and testosterone blood levels in patients with viral cirrhosis and hepatocellular carcinoma.

BACKGROUND: Patients with alcoholic cirrhosis show hypogonadism and feminization associated with sex hormone imbalance due to enhanced aromatization of testosterone and subsequent reduced testosterone and increased oestradiol blood levels. Because oestrogens modulate hepatocyte proliferation and oestrogen receptors are present in liver cirrhosis and hepatocellular carcinoma, it has been proposed that sex hormone imbalance can play a role in liver carcinogenesis. Trials with the oestrogen receptor antagonist tamoxifen have been performed with conflicting results. OBJECTIVES: To investigate oestradiol and testosterone blood levels in men with viral cirrhosis and hepatocellular carcinoma and also to investigate changes in sex hormone circulating levels induced by tamoxifen treatment. PATIENTS AND METHODS: Oestradiol and testosterone blood levels were evaluated in 32 male patients with postviral cirrhosis and hepatocellular carcinoma at the time of diagnosis and during the follow-up, and in 20 healthy controls. In eight patients, hormone levels were also assayed during treatment with tamoxifen (40 mg/day). No patient had a history of high alcohol intake. RESULTS: Oestradiol values observed at the time of diagnosis were 56.1 +/- 54.5 pmol/l, while testosterone values were 13.6 +/- 8.0 pmol/l. There was no relationship between oestrogen values and age, while higher oestradiol values were observed in patients with advanced cirrhosis (Child B and C); conversely, testosterone levels progressively and significantly decreased from cirrhosis Child A (15.1 +/- 9.7) to C (7.7 +/- 7.1) (P < 0.05). Tamoxifen treatment (40mg/day) for 1 month in eight patients increased oestradiol values (62.2 +/- 77.0 vs. 156.4 +/- 83 pmol/l, P < 0.05), while testosterone levels decreased (15.1 +/- 6.8 vs. 8.5 +/- 10.6 pmol/l). However, these changes were not associated with clinical signs or symptoms of feminization. Oestrogen levels decreased after 6 months of tamoxifen treatment. No significant change in hormone levels was observed in patients not treated with tamoxifen. Unlike patients with alcoholic cirrhosis, in male patients with viral cirrhosis and hepatocellular carcinoma there were no significant alterations in blood oestradiol and testosterone levels, although a certain degree of sex hormone imbalance was observed in those with advanced cirrhosis. Treatment with tamoxifen (40 mg/day) did not induce clinical manifestations of sex hormone imbalance.

Age Factors↗
PubMed1997

Power Doppler sonography to evaluate response to percutaneous ethanol injection in hepatocellular carcinoma.

BACKGROUND AND AIMS: The aim of the present study was to compare power Doppler imaging with traditional color Doppler imaging and with contrast enhanced computer tomography in the evaluation of intratumoral vascularity of hepatocellular carcinomas at diagnosis and in response to percutaneous ethanol injection. PATIENTS AND METHODS: Sixteen patients with hepatocellular carcinoma underwent colour Doppler, power Doppler and computed tomography at diagnosis. Seventeen patients were studied by the three techniques one month after percutaneous ethanol injection treatment. RESULTS: At baseline evaluation, power Doppler and color Doppler were always in agreement and, with the exception of one case, were also in agreement with the computerized tomography scan. On the contrary, power Doppler and computerized tomography are more sensitive than color Doppler in the evaluation of residual vascularized tumoral tissue after percutaneous ethanol injection. In 3 patients, residual vascularity was demonstrated only by computerized tomography while color and power Doppler were negative. In another 3 cases, a positive power Doppler signal, with a typical arterial Doppler spectrum, was observed while color Doppler and computerized tomography were negative. In these patients, cancer relapse was clinically evident after a few months and treatment was repeated to obtain complete necrosis. CONCLUSIONS: We conclude that only the integration of the results of all these techniques can reliably evaluate tumoral vascularity after percutaneous ethanol injection.

Adult↗
PubMed1995

Hypergastrinemia in rats with azoxymethane-induced colon cancers.

Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells.

Animals↗
PubMed1994

Proliferation and differentiation of the small intestinal epithelium: from Petri dish to bedside.

The small intestinal epithelium is a continuously renewing cell system in which two main compartments can be defined: the crypt compartment and the villus compartment. The crypt compartment houses the proliferative cells (stem cells) that give birth to the four types of differentiated enterocytes (absorptive enterocytes, goblet cells, enteroendocrine cells, Paneth cells) that, with the exception of Paneth cells, populate the villus compartment. Enterocyte proliferation, differentiation and migration are regulated by a complex network of cell-cell and cell-matrix information, and modulated by growth factors, luminal factors and, possibly, hormones. The intimate mechanisms underlying the fascinating life of the enterocytes are the object of intensive investigation although insights have come from studies "in vitro" and in transgenic animals. The enormous proliferative potential makes the small bowel an extremely plastic organ, able to adapt to various injuries and adverse conditions and to completely recover even from extensive damage. Knowledge of the biologic mechanisms of adaptation has begun to affect therapeutic approaches to a number of intestinal diseases and the future will see a significant advancement in their management. More important, understanding the molecular mechanisms regulating the perfect equilibrium between proliferation and differentiation of the intestinal enterocytes will eventually help disclose the dark side of cancer.

Cell Cycle↗
PubMed1994

Cell kinetics and polyamine enzymes in the intestinal mucosa of rats with azoxymethane induced tumours.

We studied the proliferative activity and the modifications in ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, in the apparently normal intestinal mucosae of rats with azoxymethane induced tumours. Fifty rats were treated with six weekly injections of 15 mg/kg body weight azoxymethane (AOM). Six rats died during the treatment. All the surviving rats developed intestinal tumours; tumour incidence was 93.1% (41/44) in the left colon, 40.9% (18/44) in the right colon and 45.4% (20/44) in the small bowel. In the normal-appearing mucosa close to intestinal tumours we found an extension of the normal proliferative compartment to the upper third of the crypts (stage I abnormality) and a shift of most of the DNA synthesizing cells from the basal region to the middle and upper third (stage II abnormality). Furthermore, the intestinal mucosa characterized by proliferative abnormalities showed an ODC activity significantly higher than the normal mucosa of control rats (small bowel: 1.01 +/- 0.26 vs 0.42 +/- 0.15, P < 0.01; right colon: 1.32 +/- 0.34 vs 0.25 +/- 0.02, P < 0.001; left colon: 1.93 +/- 0.35 vs 0.22 +/- 0.01, P < 0.01). We also detected a significant decrease of DAO activity in the mucosa of the small bowel and right colon of treated rats compared to controls (0.86 +/- 0.09 vs 4.39 +/- 0.85, P < 0.01; 1.04 +/- 0.43 vs 3.80 +/- 0.91, P < 0.01, respectively), while DAO activity in the left colon was unchanged. The lower incidence of tumours in the small bowel and right colon suggests the presence of factors protecting these segments from carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amine Oxidase (Copper-Containing)↗
PubMed1991

Plasma postheparin diamine oxidase in patients with small intestinal lymphoma.

Diamine oxidase (DAO) is an enzyme located almost exclusively in villus tip enterocytes. Its plasma activity is enhanced by intravenous heparin which releases the enzymes from small bowel enterocytes into the blood. Plasma postheparin DAO (PHD) values have been shown to be significantly lower in patients with malabsorption and villous atrophy, thus suggesting that PHD reflects the mature enterocytic mass. In this study we have assayed PHD in five patients with small bowel lymphoma (two with immunoproliferative small intestinal disease [IPSID] and three with non-IPSID lymphoma) associated with malabsorption syndrome and small bowel mucosa atrophy. The PHD test was performed at diagnosis, after partial or complete remission induced by chemotherapy, and during the follow-up. The PHD values, very low at diagnosis (0.66 +/- 0.12 U/ml), increased during chemotherapy and reached the normal range (greater than 3.7 U/ml) when complete remission occurred. The PHD values rapidly and consistently decreased whenever the disease relapsed. Our data indicate that in patients with small bowel lymphoma PHD test is a sensitive marker of small bowel mucosa damage and suggest that it could be useful in monitoring the recovery of mucosal lesions induced by chemotherapy.

Adolescent↗
PubMed1991

Postheparin plasma diamine oxidase values in the follow up of patients with small bowel Crohn's disease.

Measurement of postheparin plasma diamine oxidase (PHD) activity has been proposed to assess mucosal integrity in several diseases of the small intestine. In Crohn's disease, PHD values identify a group of patients with predominantly small bowel mucosal damage. To determine the role of mucosal involvement in the progression of small bowel Crohn's disease and whether different PHD values can predict different outcomes the changes in PHD values in 41 patients with small bowel Crohn's disease admitted consecutively to our department were investigated. The test was performed during periods of active disease and after either medical or surgical treatment had resulted in improvement. PHD values were significantly lower than in normal subjects (normal range 3.7-7.7 U/ml). In 35 patients with active disease (Crohn's disease activity index (CDAI) greater than 150) two groups were identified by choosing a cut off value of 2 U/ml: 93% of the 15 patients with PHD values lower than 2 U/ml (mean (SD) 1.36 (0.46) U/ml) relapsed at least once in the following year, while only the 20% of the 20 whose values were higher than 2 U/ml (mean (SD) 3.69 (1.50)) relapsed in the same period. The data were statistically significant (Yates's corrected chi 2 = 15.63; p less than 0.0001). The positive and negative predictive values of the test were 93% and 80%, respectively. During relapses, PHD values were consistently lower than previous values, and increased significantly after effective medical or surgical treatment. In the six patients in whom there were no changes in disease activity (CDAI persistently less than 150), there was no change in PHD values. This test may be useful for identifying Crohn's disease patients who are likely to relapse. Furthermore, the data indicate that mucosal damage is common in active small bowel Crohn's disease and improves at least in part after treatment.

Adult↗
PubMed1991

Effects of epidermal growth factor on diamine oxidase expression and cell growth in Caco-2 cells.

To investigate the role of diamine oxidase (DAO) in the intestinal mucosa, we compared its expression with cell proliferation and differentiation in the human colon carcinoma cell line Caco-2. DAO synthesis was evaluated in subconfluent and confluent cultures and in the presence of epidermal growth factor (EGF), a polypeptide hormone known to have specific trophic effects on the small intestinal mucosa. EGF stimulated DNA synthesis, significantly increased cellular DAO activity and the amount of enzyme secreted into the culture medium, but decreased expression of dipeptidyl peptidase IV, a marker of cell differentiation in confluent Caco-2 cells. Immunoprecipitation of DAO from cells labeled metabolically with [35S]methionine failed to demonstrate an increased enzyme synthesis in EGF-treated cells, suggesting that this hormone acted primarily at a posttranslational level by reducing DAO degradation before intracellular storage or secretion. A possible relationship between changes in cellular DAO activity and cell proliferation was also investigated by using aminoguanidine, a specific and potent DAO inhibitor. Although DAO activity was markedly suppressed, aminoguanidine had no significant effects on the rate of DNA synthesis. These results demonstrated that in Caco-2 cells EGF stimulated DNA synthesis and DAO expression; however, cell proliferation and differentiation were not correlated with the levels of cellular DAO, suggesting that this enzyme does not play a major role in the regulation of intestinal epithelial cell turnover.

Amine Oxidase (Copper-Containing)↗
PubMed1991

Therapeutic strategy for the irritable bowel syndrome.

The major aims of medical therapy in irritable bowel syndrome (IBS) are: a) to ameliorate symptoms (pain, bowel movement abnormalities, bloating) and b) to improve psychological problems of the patients. The first step of IBS therapy is the diet. In fact some forms of IBS can be ascribed to food intolerance. When abdominal pain, meteorism and constipation are the main symptoms, treatment with high-fiber diet, antispastic and antimuscarinic drugs is indicated. Sometimes amitriptyline, an antidepressant which also shows anticholinergic and analgesic properties, can be helpful. When diarrhoea is prevalent, the most effective drug is represented by loperamide. If diarrhoea is related to meal ingestion, antispastic or antimuscarinic drugs can be successfully used. In the case of diarrhoea related to documented cholorrhoea, cholestyramine can be of benefit. Furthermore, there are some resistant cases, secondary to striking psychological problems that require sedatives and antidepressant drugs and sometimes, psycho and/or hypnotherapy.

Amitriptyline↗
PubMed1990

Polarized secretion of diamine oxidase by intestinal epithelial cells and its stimulation by heparin.

The Caco-2 cells have been used as a model system to study the pathways of diamine oxidase secretion by the intestinal epithelium. When grown in Transwell filter chamber devices, the polarized cell monolayers released the enzyme preferentially into the basal chamber. Heparin (1-10 USP U/mL) rapidly induced a marked stimulation of enzyme secretion only when in contact with the basolateral cell membrane, where high affinity binding sites for [3H]heparin were also exclusively located. Among the other glycosaminoglycans tested, only heparan sulfate (150 mg/mL) was able to induce enzyme release; chondroitin sulfate (150 mg/mL) and dermatan sulfate (150 mg/mL) were without effect. Four monoclonal antibodies specific for human diamine oxidase were produced and found to immunoprecipitate a single protein with a molecular weight of 95,000 (under reducing conditions) from the culture medium of Caco-2 cells. Immunofluorescence staining of cryostat sections of human small intestine with these four antibodies localized diamine oxidase at the lateral and basal sides of the villus cells. Staining was markedly reduced in specimens obtained from patients who received doses of heparin in vivo. This study concludes that release of diamine oxidase by intestinal cells occurs specifically at the basolateral aspect of the cells, most likely through the constitutive secretory pathway. Heparin may induce its marked stimulation of enzyme release by complexing with diamine oxidase bound to the cell surface or through interaction with specific binding sites also located in the basolateral membrane. In the intestinal mucosa in vivo, the basal aspect of the villus cells represents the main site of diamine oxidase storage in the presence of normal circulating levels of heparin.

Amine Oxidase (Copper-Containing)↗
PubMed1990

Polyamine uptake by human colon carcinoma cell line CaCo-2.

The intracellular concentrations of the polyamines are highly regulated and high polyamine concentrations are associated with rapidly proliferating cells. Hormones, nutrients and growth factors that stimulate the proliferation of the intestinal epithelium, increase the intracellular polyamine concentration mainly by activating ODC expression. Other cell types stimulated to proliferate satisfy their requirement for polyamines by increasing polyamine uptake. In the present study, we investigated polyamine uptake by a human colon carcinoma cell line, CaCo-2. Uptake of putrescine, spermidine and spermine by CaCo-2 cells was saturable and temperature dependent and all polyamines appear to share a common carrier. The carrier of differentiated cells had an apparently higher affinity and lower activity than the carrier of replicating cells. Culture of CaCo-2 cells on porous filters showed that polyamine accumulation occurred mainly through the basolateral membrane in replicating cells, while an increase in the rate of apical uptake was observed after differentiation. A significant increase in polyamine uptake and in ODC expression resulted from fresh medium replacement, a well-known stimulus to proliferation; no change in uptake occurred after ODC inhibition by DFMO. We conclude that CaCo-2 cells are able to increase their polyamine concentration by both enhanced synthesis and increased polyamine uptake.

Biogenic Polyamines↗
PubMed1990

Regulation of diamine oxidase expression by ornithine decarboxylase in isolated rat small bowel enterocytes.

Ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, are highly expressed by small bowel enterocytes. Modulation of ODC expression is mediated through cellular concentration of polyamines that inhibits the enzyme synthesis and also induces the synthesis of an inhibitory protein, the antizyme, which in turn binds to ODC and inhibits its activity. DAO is an important regulator of intracellular concentration of polyamines because it catalyzes the degradation of putrescine into gamma-aminobutyraldehyde. Change in intracellular polyamine concentration has been suggested to represent a regulatory factor for DAO expression. In order to investigate a possible regulation of DAO expression by ODC, we studied the effect of difluoromethylornithine (DFMO), a selective, irreversible inhibitor of ODC, on DAO activity in isolated rat small bowel enterocytes. Our data demonstrate that in isolated small bowel enterocytes ODC inhibition by 10 mM DFMO reduced DAO activity by 53%, suggesting that, in our experimental conditions, ODC plays a regulatory role on DAO expression.

Amine Oxidase (Copper-Containing)↗
PubMed1989

Release of diamine oxidase into plasma by glycosaminoglycans in rats.

Plasma diamine oxidase (DAO) values are enhanced by intravenous injection of heparin which releases the enzyme, synthesized in small bowel enterocytes, from binding sites located on endothelial cells of the intestinal microvasculature. Intestinal DAO, in analogy with lipoprotein lipase (another heparin-released enzyme), is believed to be electrostatically linked to endothelial binding sites composed of a glycosaminoglycan (GAG) which is presumably heparan sulphate, but the complete mechanism of enzyme release is not known. In this study we assayed in rats the DAO-releasing capability of heparan sulphate, dermatan sulphate, chondroitin sulphate A and hyaluronic acid, all heparin related compounds. Heparan sulphate, a compound with the same hexosamine as heparin but with a lower concentration of sulphated iduronic acid, induced a very high release of DAO (3-fold less than heparin), while the other tested GAGs, composed of higher proportions of non sulphated uronic acid and with galactosamine instead of glucosamine, induced a significantly lower release. In rats treated with 60 mg heparan sulphate the significant decrease in ileal mucosal DAO activity indicates that, in analogy with heparin, the high plasma enzymatic activity induced is of enterocytic origin. It is suggested that the high charge density of the compounds tested, due to the degree of sulphatation, is the decisive factor in promoting the release of intestinal DAO.

Amine Oxidase (Copper-Containing)↗
PubMed1989

Modifications in enterocyte diamine oxidase distribution induced by heparin in the rat.

Heparin releases diamine oxidase (DAO) of enterocytic origin from binding sites located on small bowel microvascular endothelium. In the villus tip enterocytes the enzyme is found in organelles (about 60%) and in cytosol (about 40%), while a negligible activity is present in the brush border. In this study we assessed the changes in DAO distribution into the enterocytes induced by a high dose of intraperitoneal heparin (1000 IU) in the rat, by assaying DAO activity on subcellular fractions obtained from ileal mucosa homogenate. Heparin injection induced a marked reduction of enzyme activity in the S2 fraction (cytosol): after 30 min less than 20% of DAO activity is still found and only 8% after 150 min. In the P1 fraction (organelles) DAO activity significantly decreased only after 60 min and a further consistent reduction was recorded after 150 min. Recovery of DAO activity was complete 4 days after the injection, though it was already clearly evident in the first 2 days. These results indicate that enterocytic DAO is distributed in two different compartments: DAO located in the cytosol is quickly released by heparin, while the organelles-linked enzyme is more slowly released. The finding that recovery in DAO activity happens earlier in the P1 fraction suggests that the enzyme supplies the cytosol after being synthesized in the enterocyte organelles.

Amine Oxidase (Copper-Containing)↗
PubMed1989

Neurological and behavioral sequelae in children operated on for brain abscess.

In order to characterize neurological, intellectual and behavioral sequelae better after surgical treatment of brain abscess in childhood, 32 children were studied over a 10-year time span after treatment of a brain abscess. Depending on the clinical condition, surgical treatment consisted of simple aspiration through a burr hole or of total excision after craniotomy. There were only 3 postoperative deaths (9%). The scheduled time for long-term follow-up was 3 years after surgery. The patient assessment included information concerning the presence of seizures, accurate neurological examination, an EEG, and a battery of intellectual tests to evaluate the presence of behavioral-mental deficits. Late seizures developed in 7 of the 29 survivors. Five patients presented permanent hemiparesis after surgical treatment. It is noteworthy that the intellectual impairment observed was more severe in younger patients, while the behavioral disturbances were more marked in school-age children.

Adolescent↗
PubMed1989

Ornithine decarboxylase and diamine oxidase in human colon carcinoma cell line CaCo-2 in culture.

The human colon carcinoma cell line CaCo-2, grown in vitro under standard culture conditions and in the absence of differentiation inducers, spontaneously exhibits structural and functional characteristics of mature small bowel enterocytes. Differentiation is complete at late confluency. High activities of ornithine decarboxylase and diamine oxidase are present in enterocytes. Although these enzymes are involved in polyamine metabolism and therefore in cell replication, their function in small bowel epithelium remains to be defined. In this study ornithine decarboxylase and diamine oxidase activities were assessed in CaCo-2 cells at different stages of proliferation and differentiation. Diamine oxidase was also assayed in spent culture media to assess its spontaneous release by CaCo-2 cells. The trigger effect of medium replacement on ornithine decarboxylase activity was also investigated. Cell growth and cell cycle kinetics were determined by hemocytometric cell count and [3H]thymidine labeling index. Sucrase activity was assayed to evaluate brush-border functional maturation. Elevated ornithine decarboxylase activity was recorded during the replication phase (highest value 0.3 +/- 0.02 U/mg) characterized by high thymidine labeling index (43%), and was greatly enhanced by medium replacement (2.1 +/- 0.3 U/mg). Diamine oxidase activity was low in both cells and medium during the active phase of cell growth, and during the differentiation period it progressively increased (highest value 499 +/- 78 U/mg) along with sucrase activity. The high diamine oxidase activity recorded in the medium (highest value 1292 +/- 310 U/ml) and the evidence of diamine oxidase secretion through the basolateral membrane of the cells cultured on porous filters support the hypothesis of an extracellular role of intestinal diamine oxidase. The CaCo-2 cell line, which shows several analogies with small bowel enterocytes, can be proposed as an interesting in vitro model for studying many aspects of cell replication and differentiation depending on polyamine metabolism.

Amine Oxidase (Copper-Containing)↗