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M Fontana

Publications and source records attributed to M Fontana.

At least 19 recordsLinked to original sources
PubMed2006

Gene expression profiling of acute promyelocytic leukaemia identifies two subtypes mainly associated with flt3 mutational status.

Acute promyelocytic leukaemia (APL) is a well-defined disease characterized by a typical morphology of leukaemic cells, the presence of t(15;17) translocation and the unique sensitivity to the differentiating effect of all-trans retinoic acid. Nevertheless, some aspects are variable among APL patients, with differences substantially related to morphological variants, peripheral leukocytes count, the presence of a disseminated intravascular coagulopathy, different PML/RARalpha isoforms (long, variable or short) and Fms-like tyrosine kinase 3 (Flt3) mutations. In order to better define this variability, we investigated the gene expression profiles of 18 APL cases revealing, besides a high uniformity in gene expression pattern, the presence of few robust differences among patients able to identify, by an unsupervised analysis, two major clusters of patients characterized by different phenotypes (hypogranular M3v vs classical M3) and by the presence or absence of Flt3 internal tandem duplications (ITDs). Further supervised analysis confirmed that Flt3 status was the APL parameter best associated with these two subgroups. We identified, between Flt3 wild-type and Flt3-ITDs subsets, 147 differentially expressed genes that were involved in the cytoskeleton organization, in the cell adhesion and migration, in the proliferation and the coagulation/inflammation pathways as well as in differentiation and myeloid granules constitution suggesting a role of Flt3 mutations in the pathogenesis and clinical manifestations of APL.

Adult↗
PubMed2005

TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease.

BACKGROUND: Thiopurines are used in the treatment of inflammatory bowel disease. They are metabolised via methylation by thiopurine-S-methyltransferase (TPMT), which displays a genetically determined polymorphic activity. Subjects with reduced TPMT activity have a higher concentration of active thiopurine metabolites and may be at increased risk of bone-marrow suppression. AIMS: To evaluate the relevance of TPMT genotyping in the management of thiopurines therapy in inflammatory bowel disease patients. PATIENTS AND METHODS: Adverse effects and clinical response were determined retrospectively and correlated with TPMT genotype in 70 paediatric inflammatory bowel disease patients. RESULTS: Nineteen patients (27.1%) developed adverse effects; of the 51 who did not, 34 (66.7%) responded to treatment. Five patients (7.1%) were heterozygous for a variant TPMT allele; two of these (40%) were intolerant to thiopurines, compared to 17 of the 65 patients (26.2%) with a wild type gene (O.R. 1.88, 95% CI 0.29-12.2, p=0.61); among the 34 responders, the median dosage of the drug required to obtain remission was lower for mutated than for wild type patients (1.6mgkg(-1)day(-1) versus 2.0mgkg(-1)day(-1), p=0.043). CONCLUSIONS: There was no significant association between adverse effects of thiopurines and TPMT heterozygous genotype, but TPMT genotyping could be useful in establishing the most appropriate dose of thiopurines to start treatment.

Adolescent↗
PubMed2005

[Oral allergy syndrome and food allergy].

To obtain a precise diagnosis of food allergy, it is essential to take a careful and detailed clinical history. This allows for directing further investigations and the patient should receive adequate information. In a research setting, recombinant allergens obtained by biotechnologies permit to reach a precise identification of allergenic proteins, with the hope of treating patients exclusively with the proteins to which they are allergic. In case of light reactions, a strict allergen avoidance is not required, but it is preferable to avoid the consumption of potentially dangerous food in isolated sites and before or during physical effort. In case of severe anaphylactic reactions with potent allergens like hazelnuts, peanuts and sea food, strict information about allergen avoidance and prescription of an emergency kit will be given.

Allergens↗
PubMed2005

[Hemolytic uremic syndrome in childhood: not so rare in Swiss children].

Fifty years after the first report by Gasser and Gautier, hemolytic, uremic syndrome is rather rare but severe childhood disease. A recent survey demonstrates that more than 90% of the cases occurring in Switzerland are caused either by Escherichia coli that produces shigatoxin or by Streptococcus pneumoniae.

Escherichia coli Infections↗
PubMed2005

Biochemical properties of new synthetic carnosine analogues containing the residue of 2,3-diaminopropionic acid: the effect of N-acetylation.

Three novel carnosine analogues 7-9 containing the residue of L(+)2,3-diaminopropionic acid with different degree of N-acetylation instead of beta-alanine have been synthesized and characterized. Comparative analysis of hydrolysis by carnosinase revealed that the mono- and bis-acetylated compounds 8 and 9 are resistant to enzymatic hydrolysis and act as competitive inhibitors of this enzyme. The hydroxyl radical scavenging potential of the three analogues was evaluated by their ability to inhibit iron/H(2)O(2)-induced degradation of deoxyribose. The second-order rate constants of the reaction of compounds 7-9 with hydroxyl radical were almost identical to that of carnosine. These compounds were also found to act as protective agents against peroxynitrite-dependent damage as assessed by their ability to prevent nitration of free tyrosine induced by this species.

Acetylation↗
PubMed2004

Sorption of amines by the Langmuir-Blodgett films of soluble cobalt phthalocyanines: evidence for the supramolecular mechanisms.

By means of microgravimetry, UV-Vis spectroscopy and optic microscopy, sorption of pyridine, primary aliphatic amines and benzylamine by the Langmuir-Blodgett (LB) films of tetra-4-tert-butyl- and tetra-(3-nitro-5-tert-butyl)-substituted cobalt phthalocyanines (CoPc' and CoPc*, respectively) was studied over a broad concentration range. In general, sorption occurs as stepwise intercalation of the sorbate molecules into the supramolecular 3D structure of the phthalocyanine assembly followed by formation of the donor-acceptor complexes. Both intercalation depth and stoichiometry of the complexes are determined by the molecular structure of amines. The supramolecular factor allows discrimination between amines in air but not in aqueous solutions because of concurrent intercalation of water.

Adsorption↗
PubMed2004

Costs associated with outpatient diarrhoea in infants and toddlers: a nationwide study of the Italian Society of Paediatric Gastroenterology and Hepatology (SIGEP).

BACKGROUND: As diarrhoea mortality is negligible in Italy, other costs should be considered when planning health strategies. Little is known about the costs associated with diarrhoea in Italian children. AIMS: To assess the costs associated with outpatient infantile diarrhoea in Italy. METHODS: Primary care paediatricians from five regions filled in a questionnaire for the first 10 children (1-47 months) they visited for acute diarrhoea during a 3-month period. RESULTS: We analysed 473 questionnaires. Mean age (standard deviation) of children was 21 (11) months; mean duration of diarrhoea (standard deviation) was 4.3 (2.6) days. An overall cost of 110 (137) euro per episode was estimated, with significant difference between children younger and older than 36 months (116 euro versus 72 euro). Missed work by relatives accounts for 75% of the cost. The parents of children attending a day-care centre had an increased risk to miss work (relative risk = 2.15). A weak relationship was found between days of diarrhoea and missed work (r = 0.30); it could be estimated that the diarrhoea should be shortened by about 4 days in order to save I day of missed work. CONCLUSIONS: Acute outpatient diarrhoea is associated with a significant financial burden in Italy. Simply shortening the diarrhoea does not seem to be the most expeditious way to reduce the cost of diarrhoea itself.

Diarrhea↗
PubMed2002

Prevention of peroxynitrite-dependent damage by carnosine and related sulphonamido pseudodipeptides.

The naturally occurring dipeptides carnosine and anserine have been proposed to act as antioxidants in vivo. We investigated whether these compounds can act as protective agents able to counteract peroxynitrite-dependent reactions. The results showed that the dipeptides efficiently protect tyrosine against nitration, alpha1-antiproteinase against inactivation and human low-density lipoprotein against modification by peroxynitrite. Carnosine exerts its protective effect at concentrations similar to those found in human tissues. In addition, some synthetic pseudodipeptides, stucturally related to carnosine but stable to hydrolytic enzymes, possess protective properties against peroxynitrite-dependent damage similar to the natural dipeptides. These pseudodipeptides may represent stable mimics of the biologically active carnosine suitable for pharmacological applications.

Anserine↗
PubMed2002

The use of ciclosporin in paediatric inflammatory bowel disease: an Italian experience.

AIM: To asses the efficacy and safety of ciclosporin in a paediatric population with inflammatory bowel disease. PATIENTS AND METHODS: Twenty-three Italian children treated with ciclosporin were studied retrospectively. The indications for treatment were severe unresponsive colitis, chronic active colitis or severe fistulizing Crohn's disease. The treatment duration, follow-up and causes of drug discontinuation were assessed. RESULTS: Sixteen patients were treated intravenously for a mean time of 10 +/- 7 days (1-24 days) and 19 orally for a mean time of 133 days (17-660 days). The mean follow-up of all patients was 13.2 months. Ciclosporin was totally ineffective, being discontinued for surgery, in nine of 23 patients (39%); it was discontinued for partial response in three patients (13%). During treatment, clinical remission was achieved in eight children (35%) and maintained after drug withdrawal in four (17%). In severe unresponsive colitis, urgent colectomy was avoided in 12 (85%) of 14 patients who tolerated the drug. Side-effects appeared in six of 23 patients (26%), and three (13%) required ciclosporin to be discontinued due to neurotoxicity. CONCLUSIONS: Ciclosporin shows disappointing long-term results in the treatment of refractory inflammatory bowel disease, but can play an important role in preventing urgent surgery in unresponsive severe colitis. Severe side-effects can occur.

Adolescent↗
PubMed2001

Formation of nitrotyrosine by methylene blue photosensitized oxidation of tyrosine in the presence of nitrite.

Methylene blue photosensitized oxidation of tyrosine in the presence of nitrite produces 3-nitrotyrosine, with maximum yield at pH 6. The formation of 3-nitrotyrosine requires oxygen and increases using deuterium oxide as solvent, suggesting the involvement of singlet oxygen in the reaction. The detection of dityrosine as an additional reaction product suggests that the first step in the interaction of tyrosine with singlet oxygen generates tyrosyl radicals which can dimerize to form dityrosine or react with a nitrite-derived species to produce 3-nitrotyrosine. Although the chemical identity of the nitrating species has not been established, the possible generation of nitrogen dioxide (*NO(2)) by indirect oxidation of nitrite by intermediately produced tyrosyl radical, via electron transfer, is proposed. One important implication of the results of this study is that the oxidation of tyrosine by singlet oxygen in the presence of nitrite may represent an alternative or additional pathway of 3-nitrotyrosine formation of potential importance in oxidative injures such as during inflammatory processes.

Animals↗
PubMed2001

Interaction of enkephalins with oxyradicals.

The interaction of enkephalins (leu-enkephalin and met-enkephalin) and other tyrosine amino-terminal peptides with reactive oxygen species has been investigated. All the peptides tested exhibited hydroxyl radical and superoxide anion scavenging ability and the capacity to reduce the rate of lipid peroxidation induced by 2,2'-azobis(2-amidinopropane). The scavenging activity was observed in the 0.1-1 mM concentration range. It has been observed that enkephalins underwent an oxidative modification by Fenton systems. The tyrosine amino-terminal residue was attacked by hydroxyl radical, being converted to dopa. The overall transformation produced opiomelanin pigments. This oxidative process provides evidence of a possible route for opiomelanin synthesis without any enzyme intervention.

Antioxidants↗
PubMed2001

Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients.

BACKGROUND: Nutrient malabsorption is a negative prognostic factor in acquired immunodeficiency syndrome and recent studies have shown that pancreatic insufficiency is a codetermining factor of malabsorption. AIMS: To evaluate the effectiveness of open-label oral pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption. PATIENTS AND METHODS: Twenty-four consecutive patients with human immunodeficiency virus infection and fat malabsorption were recruited (11 males, 13 females; median age, 9.1 years). Faecal fat loss was evaluated by steatocrit assay at entry to the study (T-0), after 2 weeks (T-1) without pancreatic enzyme treatment and after a further 2 weeks (T-2) of treatment with pancreatic extracts (Creon 10 000 at a dose of 1000 units of lipase per gram of ingested dietary fat). Faecal elastase-1 and chymotrypsin were assayed at entry. RESULTS: Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration. In all patients, steatocrit values were elevated at both T-0 and T-1. Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued. In the 19 patients who concluded the study, steatocrit values during pancreatic enzyme treatment (T-2) were significantly lower than at entry (P < 0.0001). At T-2, in eight of 19 patients, steatocrit values were within the normal limit and the frequency of cases cured or improved on pancreatic enzyme therapy (at T-2) was significantly higher than that observed during the previous study period without enzyme treatment (T-1) (P < 0.01). A positive significant correlation was found between steatocrit values at entry and the Centers for Disease Control class (P < 0.0005); also, the decrease in steatocrit values during pancreatic enzyme therapy (difference between steatocrit value at T-2 and steatocrit value at T-0) positively correlated with the Centers for Disease Control class (P < 0.05). CONCLUSIONS: This pilot, open-label study showed that pancreatic enzyme supplementation therapy is highly effective in reducing faecal fat loss in human immunodeficiency virus-infected patients with nutrient malabsorption. Further double-blind studies must be undertaken to verify these results and, if they are confirmed, pancreatic enzymes can be added to our weapons in the fight against human immunodeficiency virus-associated nutrient malabsorption.

Adolescent↗
PubMed2001

[Prevalence of dyspepsia in liver cirrhosis: a clinical and epidemiological investigation].

BACKGROUND: To evaluate the prevalence and severity of dyspepsia in patients with liver cirrhosis. METHODS: A questionnaire was distributed to 33 consecutive patients suffering from liver cirrhosis (22 males and 11 females, mean age 65.5 years; 24 with post-hepatitis liver cirrhosis and 9 with alcohol- based cirrhosis) to evaluate dyspeptic symptoms. Patients receiving prolonged treatment at home with anti-acid drugs immediately prior to hospitalisation were excluded from the study. RESULTS: Twenty-eight patients complained of dyspeptic disorders. An organic cause of symptoms could not be identified in 8 patients (24.2%), whereas the following were identified as the causes of organic dyspepsia in the remaining 20 patients, in order of frequency: gastroesophageal reflux disease (55%), congestive gastropathy (40%), gastric or duodenal ulcer (30%) and gallbladder stones (35%). Lastly, a combination of at least two of these morbid conditions was found in 10 patients (50%). The severity of dyspeptic symptoms was similar in both organic and functional forms; symptoms tend to occur with moderate intensity, worsening in parallel with the aggravation of liver disease. CONCLUSIONS: Dyspepsia is a very frequent phenomenon in cirrhotic patients; it is normally sustained by an organic cause. The predominance of functional forms in liver cirrhosis is practically the same as that reported in the general population.

Aged↗
PubMed2001

Clinical applications and outcomes of using indicators of risk in caries management.

The aim of this review was to systematically assess clinical evidence in the literature to determine the predictive validity of currently available multivariate caries risk-assessment strategies (including environmental, sociodemographic, behavioral, microbiological, dietary/nutritional, and/or salivary risk factors) in: 1) primary teeth; 2) coronal surfaces of permanent teeth; and 3) root surfaces of permanent teeth. We identified 1,249 articles in the search, and selected 169 for full review. Inclusion and exclusion criteria were established prior to commencement of the literature search. Papers that conformed to these criteria were included (n = 15 for primary teeth; n = 22 for permanent teeth; and n = 6 for root surfaces), and 126 papers were excluded. Included articles were grouped by study design as: longitudinal, retrospective, and cross-sectional. The predictive validity of the models reviewed depended strongly on the caries prevalence and characteristics of the population for which they were designed. In many instances, the use of a single predictor gave equally good results as the use of a combination of predictors. Previous caries experience was an important predictor for all tooth types.

Adolescent↗
PubMed2000

Hypotaurine and superoxide dismutase: protection of the enzyme against inactivation by hydrogen peroxide and peroxidation to taurine.

Hypotaurine is able to prevent the inactivation of SOD by H2O2. The protection is concentration-dependent: at 20 mM hypotaurine the inactivation of SOD is completely prevented. It is likely that hypotaurine exerts this effect by reacting with hydroxyl radicals, generated during the inactivation process, in competition with the sensitive group on the active site of the enzyme. According to this, spectral studies indicate that in presence of hypotaurine the integrity of the active site of SOD is preserved by the disruptive action of H2O2. An interesting outcome of the SOD/H2O2/hypotaurine interaction is that SOD catalyzes the peroxidation of hypotaurine to taurine. Indeed, the formation of taurine increases with the reaction time and with the enzyme concentration. Although the peroxidase activity of SOD is not specific and relatively slow compared to the dismutation of superoxide, it might represent another valuable mechanism of production of taurine.

Animals↗