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Biomedical subjects

G Di Stefano

Publications and source records attributed to G Di Stefano.

At least 19 recordsLinked to original sources
PubMed2006

Doxorubicin coupled to lactosaminated albumin: Effects on rats with liver fibrosis and cirrhosis.

BACKGROUND: The conjugate of doxorubicin with lactosaminated human albumin has the potential of increasing the doxorubicin efficacy in the treatment of hepatocellular carcinomas expressing the asialoglycoprotein receptor. However, coupled doxorubicin also accumulates in the liver, which might damage hepatocytes. AIMS: To verify whether coupled doxorubicin impairs liver function in rats with liver fibrosis and cirrhosis. METHODS: Coupled doxorubicin was administered using the same schedule which exerted an antineoplastic effect on rat hepatocellular carcinomas (4-weekly injections of doxorubicin at 1 microg/g). Liver fibrosis/cirrhosis was produced by carbon tetrachloride (CCl4) poisoning. Liver samples were studied histologically. Serum parameters of liver function and viability were determined. RESULTS: In normal rats, administration of coupled doxorubicin neither caused microscopic changes of hepatocytes nor modified serum liver parameters. In rats with fibrosis/cirrhosis, although a selective doxorubicin accumulation within the liver followed coupled doxorubicin administration, the drug did not have a detrimental effect on the histology of the liver and, among serum liver tests, only alanine aminotransferase and aspartate aminotransferase levels were moderately modified. CONCLUSIONS: Coupled doxorubicin can be administered to rats with liver fibrosis/cirrhosis without inducing a severe liver damage. If further studies will confirm the efficacy and safety of this compound, coupled doxorubicin therapy may open a new perspective in the treatment of hepatocellular carcinoma.

Animals↗
PubMed2006

Structural synaptic remodeling in the perirhinal cortex of adult and old rats following object-recognition visual training.

The ultrastructural features of layer II synapses in the perirhinal cortex of adult (4- to 6-month-old) and old (25- to 27-month-old) rats exposed to a six-session object recognition visual training were investigated by morphometric methods. The comparative analysis showed a higher synaptic numeric density, a lower synaptic average area, and a lower percentage of megasynapses (S > 0.5 microm2) in old trained rats versus controls, and a higher percentage of small (S < 0.15 microm2) junctions in adult trained rats versus controls. The more marked synaptic remodeling underlying memory consolidation in the perirhinal cortex of old rats might reflect a pre-existing lower dynamic status.

Aging↗
PubMed2006

[Gastrointestinal stromal tumors: report of three cases and review of the literature].

Gastrointestinal stromal tumours are the most common mesenchimal tumours of the gastrointestinal tract. Diagnosis of these tumours is difficult to establish, because symptoms are vague and traditional diagnostic tests are not specific. Natural history remains poorly defined and many criteria have been correlated with prognosis; for instance, some authors have found that GIST localization influences clinical behavior, that has not been confirmed by other authors; actually, tumour size, mitotic rate and complete resection seem to be the main prognostic factors. Surgical resection is the treatment of choice, with little efficacy reported for irradiation, conventional cytotoxic agents or both. Nevertheless, imatinib mesylate has recently demonstrated significant activity and tolerability in the treatment of malignant unresectable or metastatic GIST. Three cases of GIST, complicated by intestinal bleeding and intestinal obstruction respectively, are presented and a review of the literature is made.

Aged↗
PubMed2004

Immunodeficiency in different histotypes of radically operable gastrointestinal cancers.

Cell-mediated immunodeficiency, with Total and T lymphocytes count decrease, is well established in cancer patients and it predicts a poor prognosis and poor survival rates. Furthermore, major surgery induces a transient immunodeficiency, too. Nevertheless, cell-mediated immunity in pancreatic cancer, which has a very poor prognosis, has not been completely outlined. Aim of this study is to evaluate the cell-mediated IL-2 dependent immune status in operable pancreatic cancer patients and to compare it with other gastrointestinal tumors. One hundred and twenty-one cancer patients (22 pancreatic, 48 gastric and 51 colorectal), with a median age of 66 years (range 42-83), 55 males and 66 females, were enrolled. Total lymphocyte count and lymphocytes subset (T helper count - CD4+) were assessed preoperatively and on the 14th and 50th postoperative day. Results obtained were compared between the groups and related to nodal involvement (N0 versus N+). Colorectal and gastric cancer patients showed quantitative lymphocyte deficiency at baseline in 29% and 41% of cases, respectively. Fourteen days after surgery values below normal range were found in 44% and 54% (Total) and 53% and 67% (T helper), respectively. Recovery of postoperative surgery-related lymphocytopenia occurred late only in patients with normal count at baseline. According to regional nodal involvement (pN0/N+) T helper deficiency was significantly more frequent in patients with nodal involvement than in patients without. In pancreatic cancer, percentage of immunodepressed patients at baseline was higher compared to the other two groups (71%). Lymphocyte count was significantly different between pancreatic and gastric/colorectal cancer, reaching a statistical significance at baseline and on the 14th and 50th postoperative day. No differences of T helper deficiency were noted according to nodal involvement (N0 versus N+) neither at baseline nor in the postoperative period. In conclusion, the degree of immunosuppression varies among different tumor types: since initial stages of disease, immunodepression was significantly greater in pancreatic cancer which should be considered always a systemic disease even in early stages and indipendently from the nodal involvement and from tumor load.

Adenocarcinoma↗
PubMed2003

Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier.

BACKGROUND: The hepatocyte receptor for asialoglycoproteins, which binds and internalises galactosyl terminating peptides, was found to be expressed also on the cells of the majority of hepatocarcinomas. AIMS: To verify whether doxorubicin coupling to lactosaminated albumin, a galactosyl terminating neoglycoprotein, produces selective drug accumulation in hepatocytes with reduced concentrations in extra-hepatic tissues, thus facilitating the use of the drug in hepatocarcinoma treatment. METHODS: Doxorubicin concentrations were measured in organs of mice injected with the free or coupled drug. RESULTS: In mice injected with the coupled drug, the ratios between doxorubicin concentrations in liver and those in heart, intestine, spleen and kidney were 8-14 times higher than in animals that received the same dose of the free drug. CONCLUSIONS: Due to the very efficient liver targeting of doxorubicin, the lactosaminated human albumin-doxorubicin conjugate appears to have the potential of improving the chemotherapy of hepatocellular carcinomas through the asialoglycoprotein receptor.

Animals↗
PubMed2003

Epidemiology of overweight and obesity among school children and adolescents in three provinces of central Italy, 1993-2001: study of potential influencing variables.

OBJECTIVE: The prevalence of overweight and obesity was estimated among the school children and adolescents of three provinces of central Italy, and the role of several possible influencing factors was analysed. DESIGN, SUBJECTS AND MEASUREMENTS: Body mass index (BMI) was measured in 44 231 subjects, age 3-17.5 y, and a household questionnaire was filled out by the parents of 12 143 subjects to collect the following data: subjects, only child or firstborn status, prematurity, birth weight, type of feeding until the fifth month, menarche status in girls; parents, age at the time of the subject's birth; BMI (mean of the two parents) at the time the subject was measured, mother's age of menarche, socioeconomic status. BMI was measured in a subgroup of 10 795 subjects 1 y later to study the yearly sex- and age-related variations from the categories of normal weight to overweight or obesity and vice versa. All females aged 11-14 y were asked if they had their menarche. RESULTS: Striking differences in the proportions of overweight and obesity resulted from the use of two different criteria for defining cutoff points. The overall prevalence of overweight was 13.2 and 20.7% in males, and 13.7 and 18.6% in females, and the overall prevalence of obesity varied between 24.2 and 6.3% in males, and between 22.9 and 6.1% in females, respectively. Parents' BMI, birth weight, firstborn status and post-menarche status in girls showed a significant association with overweight and/or obesity in logistic regression models. CONCLUSIONS: A large prevalence of overweight and obesity was observed in school subjects from three provinces of central Italy. From the comparisons of the prevalence rate, the new internationally agreed criteria seem more appropriate for epidemiological studies in this population. SPONSOR: University of Perugia, Region of Umbria, Commune of Perugia.

Adolescent↗
PubMed2003

Ethanol-induced decrease of the expression of glucose transport protein (Glut3) in the central nervous system as a predisposing condition to apoptosis: the effect of age.

We measured the effect of chronic ethanol administration on the expression of Glut3 in the cerebellum and hippocampus of adult and old rats. Glut3 expression significantly decreased in aging, in ethanol-treated rats vs. age-matched controls, and in adult- vs. old ethanol-treated rats. These findings lend consistent support to the hypothesis that disturbances of glucose metabolism due to ethanol may constitute an unfavorable condition predisposing to neuronal death.

Aging↗
PubMed2002

Floxuridine coupling with lactosaminated human albumin to increase drug efficacy on liver micrometastases.

BACKGROUND: Conjugates of nucleoside analogues with galactosyl terminating peptides selectively enter hepatocytes through the asialoglycoprotein receptor. After intracellular release from the carrier, the drugs partly exit from hepatic cells into hepatic blood. AIMS: To establish whether administration of a conjugate of floxuridine with lactosaminated human albumin selectively enhances drug concentrations in hepatic blood. Floxuridine is a fluoropyrimidine active on human colorectal cancer, a tumour which metastasises first to the liver. METHODS: In rats injected with free or conjugated floxuridine, plasma levels of the drug were determined in hepatic veins and in inferior vena cava, in order to measure drug concentrations in hepatic blood and in the systemic circulation, respectively. RESULTS: Ratios between floxuridine levels in hepatic veins and those in systemic circulation were found to be seven times higher in rats injected with the conjugate (p=0.000). CONCLUSIONS: The present results suggest that coupling to lactosaminated albumin might improve the effect of floxuridine in adjuvant chemotherapy of colorectal cancer by exposing the cells of liver micrometastases (nourished by hepatic sinusoids) to enhanced drug concentrations.

Animals↗
PubMed2002

Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjögren's syndrome patients.

AIM: To study the effect of the treatment of dry eye in Sjögren's syndrome patients with hypotonic or isotonic hyaluronate eye drops. METHODS: 40 Sjögren's syndrome patients were divided in two groups and treated as follows: group 1 with hypotonic (150 mOsm/l) 0.4% hyaluronate eye drops; group 2 with isotonic 0.4% hyaluronate eye drops. The eye drops were instilled six times a day for 90 days. Grading of subjective symptoms, break up time (BUT), corneal fluorescein staining, conjunctival rose bengal staining, Schirmer's I test, and conjunctival impression cytology were carried out at 0 and 15, 30, 90 days from the beginning of the study. Patients were examined in a blind fashion. For the statistical analysis the Student's t test, Mann-Whitney U test, and chi(2) test were performed. RESULTS: Symptoms were statistically significantly improved at day 15 in both groups but group 1 patients had a global score statistically significantly better group 2 (p=0.02). At day 15 group 1 patients had an improvement from baseline values of BUT (p=0.003), fluorescein, and rose bengal score (p=0.000001 and p=0.0004 respectively). Group 2 patients had, at day 15, an improvement of BUT and fluorescein score compared to baseline values (p=0.05 and p=0.0001 respectively). A comparison between the two groups showed better results for group 1 patients at day 15 for rose bengal stain (p=0.01) and for BUT (p=0.05) and fluorescein score (p=0.0003) at day 90. The conjunctival impression cytology showed that group 1 had a statistically significant better total score than group 2 starting from day 15 and lasting throughout the study (p<0.02). Also group 2 patients showed an improvement from baseline values starting from day 30 (p=0.000005). CONCLUSION: Hyaluronate eye drops are useful for treating severe dry eye in Sjögren's syndrome patients. The use of a formulation with pronounced hypotonicity showed better effects on corneoconjunctival epithelium than the isotonic solution.

Adult↗
PubMed2001

Coupling of 5-fluoro 2'-deoxyuridine to lactosaminated poly-l-lysine: an approach to a regional, non-invasive chemotherapy of liver micrometastases.

Nucleoside analogs conjugated with galactosyl-terminating peptides selectively enter liver cells and after intracellular release from the carrier partly exit into bloodstream, resulting in higher concentrations in liver blood than in systemic circulation. The aim of the present experiments was to ascertain whether, in mice injected with non-toxic doses of a 5-fluoro 2'-deoxyuridine (FUdR) conjugate with lactosaminated poly-L-lysine (L-poly(LYS)), the drug was released by hepatic cells in high enough amounts to be pharmacologically active on neoplastic cells infiltrating the liver. We observed that L-poly(LYS)-FUdR inhibited the growth of hepatic metastases induced by intrasplenic administration of murine colon carcinoma C-26 cells. L-poly(LYS)-FUdR was not toxic for C-26 cells in vitro, was selectively taken up by mouse liver, and was stable in mouse blood, indicating that the effect on the metastases was due to FUdR (and/or its active metabolites) released in liver blood after the conjugate was taken up by the hepatic cells. These results suggest that L-poly(LYS)-FUdR might be useful in adjuvant chemotherapy of tumors giving liver metastases. The drug released from hepatic cells into liver blood following conjugate administration via the peripheral venous route might accomplish a locoregional, non-invasive treatment of micrometastases nourished by liver sinusoids.

Amino Sugars↗
PubMed2001

Symptomatic approach to posttraumatic headache and its possible implications for treatment.

We investigated 112 patients [mean age 39.5 +/- 10.5 years, 59% women (n=66)] with chronic posttraumatic headache following cranio-cervical acceleration/deceleration trauma after an average time interval of 2.5 +/- 1.9 years from trauma. Headache following minor head injury or whiplash is one of the most prominent problems in neurotraumatology. Previous research is inconclusive regarding the symptomatic approach of this type of headache. Details of the phenomenology of posttraumatic headache in the previous literature are inconclusive. This may lead to inappropriate treatment strategies, because recent advances in therapy of different headache types may be neglected. Patients were investigated at the outpatient service of the Department of Psychiatry. Headache was analyzed according to its principal location, laterality, projection, quality, precipitation or aggravation and possible additional symptoms. For this analysis, headache was diagnosed according to the classification of the International Headache Society. The results showed that 42 patients (37%) had tension-type headache, 30 (27%) were identified as suffering from migraine, whereas 20 patients (18%) had cervicogenic headache. An additional 18% of patients suffered from headache that did not fulfill criteria of a particular category. In 104 patients (93%), neck pain was associated in time with headache. Each of the diagnosed headache types in this study may require specific treatment strategies based upon empirical studies of non-traumatic headache types. For these reasons a detailed analysis of headache following cranio-cervical acceleration/deceleration trauma is necessary.

Adult↗
PubMed2001

Age-related effects of moderate alcohol consumption on GAP-43 levels in rat hippocampus.

The effects of moderate intake of ethanol and ageing were investigated on the levels of the growth-associated protein GAP-43, whose expression has been used as an indicator of axonal growth during development, regeneration and remodelling of synaptic connections. Groups of female Wistar rats (12 and 24 months of age), were alcohol-fed for one month while age-matched control groups received an isocaloric diet. A quantitative evaluation of GAP-43 was performed in hippocampus and in hippocampal selected areas in view of the vulnerability of this complex to alcohol aggression by means of two different methods, namely Western blot analysis and immunohistochemistry. While the former measures total extractable GAP-43, the latter allows visualisation of in situ changes in topographical distribution of GAP-43. Western blot analysis revealed an age-dependent reduction (-47%) and an ethanol-associated increase (81%) of GAP-43 demonstrated only in the old group. Conversely, quantitative immunohistochemistry of GAP-43 in the entire hippocampus showed a non-significant ethanol-related decrement in 24-month-old rats (-30%), although the age-dependent reduction was confirmed. Ageing was associated with a decrement of GAP-43 immunostaining in CA3 stratum radiatum (CA3) and in inner molecular layer of dentate gyrus (IML). Treatment determined a decrease of GAP-43 immunostaining in adult rat CA3 and IML and no change in CA1 stratum radiatum (CA1). Our results suggest that immunohistochemistry evaluation underestimates GAP-43 levels in ethanol-treated animals possibly as a consequence of conformational changes induced by alcohol, resulting in non-targeting of the specific antibody. Western blot analysis demonstrate that although there is a reduction of GAP-43 levels in hippocampus of aged rats, this structure retain a remarkable potential to compensate for ethanol toxicity during ageing.

Aging↗
PubMed2001

Long-term efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. An Italian multicenter, randomized trial.

BACKGROUND/AIMS: To evaluate the therapeutic efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. METHODS: One hundred and fifty-one patients were randomly assigned to receive either recombinant interferon alpha-2b (nine million units three times per week) and lamivudine (100 mg/daily per os) for 24 weeks or lamivudine alone (100 mg/daily per os) for 52 weeks. Patients were followed up for a further 48 weeks. RESULTS: Sustained HBeAg seroconversion with undetectable serum levels of HBV DNA was observed in 25 of 76 patients (33%) treated with the combination therapy and in 11 of 75 patients (15%) treated with monotherapy (P=0.014). Histological improvement defined as a reduction of at least two points in the inflammation score as compared with pretreatment score was observed in 35 of 76 patients (46%) treated with combination therapy and in 20 of 75 patients (27%) treated with monotherapy (P=0.021). Both therapeutic regimens were well tolerated. CONCLUSIONS: Six-month treatment with interferon alpha-2b and lamivudine in combination appeared to increase the rate of sustained HBeAg seroconversion compared to 1-year lamivudine monotherapy. However, the potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy.

Adult↗
PubMed2001

Quantitative cytochemical mapping of mitochondrial enzymes in rat cerebella.

Mitochondrial metabolic competence, defined as the organelle's capacity to provide adequate amounts of ATP in due time, appears to constitute an important determinant in several biological processes and pathological conditions. Thus, the assessment of the metabolic efficiency of the mitochondrial population in a given tissue area or cellular compartment may provide clues to identifying alterations of the cellular bioenergetic machinery, which may constitute a predisposing condition leading to impaired organ and system functions. In the cerebellar cortex of adult rats, the activities of the enzymes cytochrome oxidase (COX) and succinic dehydrogenase (SDH) were, respectively, evidenced by means of the diaminobenzidine and copper ferrocyanide preferential cytochemical techniques. At the electron microscope, the activities of these two key molecules of the respiratory chain were clearly visualised as dark precipitates at the inner mitochondrial membrane sites where COX and SDH are located. By means of the disector method, unbiased mitochondrial samplings were carried out to measure: the number of mitochondria/microm(3) of tissue (numeric density: Nv); the mitochondrial volume fraction/microm(3) of tissue (volume density: Vv) and the average mitochondrial volume (V) both on COX- and SDH-positive organelles in the cerebellar glomeruli and Purkinje cells, respectively. The ratio R (total area of the precipitates due either to COX or SDH activity within the single mitochondrion/area of the same organelle) was also evaluated to get information on the enzyme activity related to mitochondrial size.The documented accumulation of mutant mitochondrial DNA particularly in postmitotic cells results in a marked heteroplasmy (mixtures of normal and mutated genomes) at mitochondrial and cellular levels, thus the cellular potential for energy production is demanded to a mosaic of organelles with different functional capabilities. Assessment of the mitochondrial mosaic outline by means of quantitative cytochemistry of key enzymes of the respiratory chain, such as COX and SDH, may allow for the morphofunctional metabolic mapping of mitochondrial efficiency in discrete cellular or tissue compartments.

Animals↗
PubMed2001

Quantitative immunohistochemistry of glucose transport protein (Glut3) expression in the rat hippocampus during aging.

Immunohistochemistry of Glut3 (45 kD), an integral membrane peptide mediating the transport of glucose in neurons, was carried out in the hippocampus of 3- and 28-month-old rats to assess the effect of age on energy metabolism. Free-floating sections of fixed-frozen hippocampi were processed for quantitative immunohistochemistry of Glut3. A rabbit affinity-purified antibody identified Glut3 immunoreactivity. Glut3 staining was intense in neuropil, axons, and dendrites, whereas nerve cell bodies were unstained. With aging, Glut3 reactivity was significantly decreased in the inner molecular layer of the hippocampal dentate gyrus (-46%) and the mossy fibers of the CA3 sector (-34%), whereas the stratum radiatum of CA1 did not show any difference due to age. These data document an age-dependent decrease in Glut3 expression in discrete areas of rat hippocampus. Glut3 constitutes the predominant glucose transporter in neurons and is found abundantly in regions with high synaptic density characterized by frequent bursts of function-adequate metabolic activity. Our findings therefore lend further support to the critical role of an impaired metabolism in age-related brain dysfunctions and disease.(J Histochem Cytochem 49:671-672, 2001)

Aging↗
PubMed2001

Distribution of map2 in hippocampus and cerebellum of young and old rats by quantitative immunohistochemistry.

The microtubule-associated protein MAP2 is a cytoskeletal protein that plays a regulatory role in neuronal plasticity and in maintaining the morphology of differentiated neurons. MAP2 distribution was assessed in hippocampus and cerebellum of young and old rats by quantitative immunohistochemistry. In old vs young rats, densitometric analysis showed a significant decrease of MAP2 immunoreactivity in the hippocampus CA1 field (-93%), whereas no difference was found in cerebellar MAP2 distribution. These preliminary data suggest that in areas of the brain involved in memory acquisition and consolidation, MAP2-dependent neuroplasticity and structural integrity are significantly decreased in aging.

Aging↗