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Biomedical subjects

S Monti

Publications and source records attributed to S Monti.

At least 37 records · Page 2Linked to original sources

S-adenosyl-L-methionine: role in phosphatidylcholine synthesis and in vitro effects on the ethanol-induced alterations of lipid metabolism.

Hepatic lipid metabolism is extremely modified by excessive ethanol consumption, but the cellular mechanisms of such alterations are still largely unexplored. S-Adenosyl-L-methionine (SAMe) is known as an important methylating agent and as a precursor of glutathione and it has been shown to prevent some of the toxic effects of ethanol in the liver. We therefore studied the effects of ethanol on cholesterol synthesis in a human hepatomal cell line (HepG2), the kinetics of SAMe, and its putative protective effects on the alterations of lipid metabolism induced by toxic concentrations of alcohol. Incubation of HepG2 cells with [3H]SAMe resulted in a progressive increase in the labelling of phosphatidylcholine and of its two intermediates during synthesis starting from phosphatidylethanolamine. This process is enzymatic, since it does not take place in heat-inactivated cells. Also, ethanol induced an increase in cholesterol and triglycerides syntheses and a decrease in phospholipid labelling. These alterations were not prevented by SAMe 10(-4) M, indicating that the protective effects of the drug are related to other mechanisms of action such as reduced formation of collagen, restoration of glutathione levels, and normalization of membrane functions.

Acetates↗

Ethanol enhances cholesterol synthesis and secretion in human hepatomal cells.

Excessive consumption of alcohol leads to severe alterations of lipid metabolism, including hyperlipemia and hypercholesterolemia. Following these epidemiological observations, we investigated the effects of ethanol at the cellular level by employing a human hepatomal cell line (HepG2) and by evaluating the biosyntheses of lipid classes from different labeled precursors. Incubation of cells with 2% ethanol resulted in a decreased labeling of phospholipids and in an increase in cholesterol synthesis and secretion. Triglyceride synthesis was increased by ethanol but their secretion in the medium was reduced, suggesting that these alterations may be related to their accumulation in the liver. The alcohol-induced alterations of lipid metabolism are not due to its metabolite acetaldehyde and data suggest that alcohol enhances cholesterol synthesis by affecting the initial steps without increasing HMGCoA expression. The observed modifications of lipid metabolism in HepG2 may partially explain the enhanced incidence of cardiovascular disorders that has been associated with alcoholism.

Acetates↗

pH effects on the spectroscopic and photochemical behavior of enoxacin: a steady-state and time-resolved study.

The spectroscopic and photochemical behavior of Enoxacin (ENX), 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)- 1,8-naphthyridine-3-carboxylic acid, has been investigated in aqueous solutions between pH 3.5 and pH 12. The absorption and emission properties of ENX are strongly affected by pH. The fluorescence quantum yield, 4 x 10(-3) at pH 3.5, increases by a factor of two on going to neutral pH while a strong reduction is observed at alkaline pH. The photodegradation quantum yield also depends on pH, being maximum in neutral conditions (ca 0.04). Nanosecond flash photolysis experiments confirm that the yield of absorbing transients is maximum at neutral pH while it decreases to zero at acid and alkaline pH. These results indicate that both the dissociation of the carboxylic group and the protonation of the piperazinyl residues are key steps for the formation of the photochemically active form of ENX. Loss of F by heterolytic cleavage of the C-F bond is proposed to occur from the triplet state of the zwitterion with formation of a carbocation. A path for the evolution of this intermediate to the final product is also proposed.

Anti-Infective Agents↗

Triplet photoreactivity of the diaryl ketone tiaprofenic acid and its decarboxylated photoproduct. Photobiological implications.

The 2-benzoylthiophene chromophore of the photosensitizing drug tiaprofenic acid and of its decarboxylated derivative is characterized by a unusually high energy gap between the T1 (pi, pi*) and T2 (n, pi*) excited states, which makes this a unique system to study the intrinsic photoreactivity of the two states. Weak fluorescence and phosporescence emission were detected at room temperature. Tiaprofenic acid undergoes photodecarboxylation from the triplet manifold as the main reaction. The photoprocess is temperature dependent with activation energy of 7-10 kcal/mol, close to the energy gap between T1 and T2. The decarboxylated product abstracts hydrogen in type I reactions. The involvement of T2 in the above processes is proposed. Moreover the decarboxylated derivative exhibits reactivity toward phenols, consistent with a participation of the T1 state as electron acceptor. The observed photoprocesses can account for biological photosensitization reactions, like membrane damage and protein modification.

Decarboxylation↗

Triplet photochemistry of suprofen in aqueous environment and in the beta-cyclodextrin inclusion complex.

The photodecarboxylation of suprofen in the carboxylate form was studied in aqueous medium as a function of the temperature, the concentration and the presence of oxygen by steady-state and time-resolved photochemical techniques. The process is characterized by an activation energy of 9-10 kcal/mol, the precursor state being the lowest triplet which is of pi-pi* nature. The reactivity of the drug was also studied in the beta-cyclodextrin inclusion complex and an additional photoreaction involving the macrocycle as reactive species was observed. Representative NMR and circular dichroism measurements were performed. Singlet molecular oxygen formation was also investigated.

Anti-Inflammatory Agents, Non-Steroidal↗

The impact of modeling the dependencies among patient findings on classification accuracy and calibration.

We present a new Bayesian classifier for computer-aided diagnosis. The new classifier builds upon the naive-Bayes classifier, and models the dependencies among patient findings in an attempt to improve its performance, both in terms of classification accuracy and in terms of calibration of the estimated probabilities. This work finds motivation in the argument that highly calibrated probabilities are necessary for the clinician to be able to rely on the model's recommendations. Experimental results are presented, supporting the conclusion that modeling the dependencies among findings improves calibration.

Bayes Theorem↗

Phase I-II study of vinorelbine in combination with 5-fluorouracil and folinic acid as first-line chemotherapy in metastatic breast cancer: a regimen with a low subjective toxic burden.

BACKGROUND: Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable toxicity profile. Its combination with other effective and well-tolerated cytotoxics may thus be beneficial. We investigated the therapeutic effect of a combination of vinorelbine plus 5-fluorouracil and folinic acid as first-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Forty-five patients with advanced or metastatic breast cancer were enrolled in this phase I-II study and treated with 5-fluorouracil (350 mg/m2 i.v. on day 1 to 3), folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine given on days 1 and 3 at the dose of 25 mg/m2 (dose level 1), or 30 mg/m2 (dose level 2). Therapy was given on an outpatient basis every three weeks. RESULTS: Phase I: Dose limiting toxicity (DLT) occurred at the second dose level of vinorelbine (30 mg/m2), with two out of three patients developing severe constipation ('ileus-like syndrome' grade 4), and fever (grade 2). Consequently, the dose evaluated in the phase II study was 25 mg/m2. Phase II: Objective responses were observed in 24 of 39 evaluable patients (95% confidence interval (95% CI), 47% to 77%). There were seven complete responses (18%), 17 partial responses (44%), and for nine patients (23%) disease was stable. Only six patients (15%) experienced disease progression. The median response duration was 10 months (range 6 to 24+) and the median time to progression was eight months (range 2 to 24+). Granulocytopenia was the most frequently observed side effect, with a grade 4 nadir being observed in 30 patients (77%), with four hospital admissions due to febrile neutropenia. Nausea, vomiting, and anorexia were mild to moderate and reported by less than half of the patients. Alopecia was moderate and occurred in about one-third of the patients. The other side effects were mild and easily manageable. CONCLUSIONS: This effective combination chemotherapy of vinorelbine, 5-fluorouracil and folinic acid is comparable to other first-line regimens in terms of efficacy, and is subjectively well tolerated, thus deserving a test in randomized trials in the advanced and adjuvant settings.

Adult↗

Lazaroid U-74389F attenuates phorbol ester-induced lung injury in rabbits.

We examined the effect of the antioxidant lazaroid U-74389F on acute lung injury induced in rabbits by phorbol myristate acetate (PMA). Thirty minutes after receiving either U-74389F (15 mg.kg-1 i.v.) or U-74389F vehicle, rabbits (n = 60) were given PMA (60 micrograms.kg-1 i.v.). PMA vehicle injected rabbits (n = 20) served as controls. Over a 5 h period after PMA or PMA vehicle injection, we measured arterial pH, arterial oxygen tension (Pa,O2), arterial carbon dioxide tension (Pa,CO2), and the plasma concentration of the neutrophil chemoattractant interleukin-8 (IL-8). At postmortem, lungs were inspected for macroscopic injury and examined histologically. Malondialdehyde levels were assayed in lung tissue as an index of lipid peroxidation. In bronchoalveolar lavage (BAL), total and differential cell counts, protein and IL-8 concentrations were measured. Compared to normal controls, rabbits challenged with PMA alone developed arterial acidosis, hypercapnia and hypoxaemia, accompanied by significant rise in plasma IL-8 concentration. U-74389F pretreated animals did not develop significant arterial blood gas abnormalities and had significantly lower IL-8 concentration in plasma. U-74389F did not prevent PMA-induced lipid peroxidation. However, macroscopic signs of lung injury and the degree of alveolar haemorrhage and protein extravasation were significantly less severe in pretreated rabbits than in those given PMA alone. In addition, U-74389F significantly reduced IL-8 concentration and neutrophil number in BAL. By histological assessment, 80% of lung neutrophils were localized in alveolar spaces of animals receiving PMA alone. Conversely, in U-74389F pretreated animals, 75% of neutrophils were distributed within extra-alveolar blood vessels and alveolar septa. We conclude that lazaroid U-74389F attenuates lung injury in rabbits given PMA by preventing neutrophil migration into pulmonary alveoli. This effect may, in part, be related to downregulation of IL-8 production.

Animals↗

Mitochondria act as a reservoir for the basic amine HIPDM in the lung.

The lungs are a site for the uptake, accumulation, and storage of exogenous basic amines. The compound N-N-N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3 propanediamine (HIPDM) is a basic amine that can be labelled with radioactive iodine and detected by external counting. Intravenously injected 123I-HIPDM is extracted by the human lung, where it is retained in a slowly effluxable pool. In the present study, we measured HIPDM lung kinetics and subcellular distribution in rabbits given i.v. 125I-HIPDM. Rabbits were killed from 2 min to 5 h after injection, and the radioactivity retained in their lungs was measured. Subcellular lung fractions (nuclear, mitochondrial, lysosomal, microsomal and postmicrosomal supernatant) were assayed for HIPDM radioactivity, protein content, and distribution of specific marker enzymes. HIPDM lung clearance in rabbits was nearly identical to that of humans. Virtually all the HIPDM radioactivity in lungs (98+/-1%) was associated with subcellular membranous structures. The highest HIPDM specific radioactivity was found in the mitochondrial fraction, and the subcellular distribution profile closely resembled that of the mitochondrial marker enzyme succinate cytochrome c reductase. No redistribution of HIPDM among subcellular compartments was observed over a 5 h period after injection. The data indicate that mitochondria act as reservoir for HIPDM in the lungs and contribute to the pulmonary persistence of this compound. HIPDM can be used to investigate the pulmonary uptake of basic amines in health and in lung disease.

Animals↗

Helicobacter pylori infection in families of Helicobacter pylori-positive children.

Relatives of Helicobacter pylori positive patients show a higher incidence of Helicobacter pylori infection than the general population, probably due to relapses and/or reinfections between members of the family. Aim of this study was to evaluate the prevalence of the infection in 121 relatives of 41 children with Helicobacter pylori positive gastritis. Specific IgG antibodies (ELISA) were evaluated, and bacteria on gastric biopsy specimens were investigated by urease-rapid test, culture test and GIEMSA or acridine orange staining. Of the eighty-two relatives, 68% were antibody positive. Thirty-five agreed to undergo endoscopy. With the exception of one brother, all subjects (97%) were found to be infected by Helicobacter pylori. Two symptomatic relatives, with normal antibody titres, were submitted to endoscopy and found to be colonized by Helicobacter pylori. The present data confirm the high prevalence of infection within families and appear to demonstrate the usefulness of endoscopy for all subjects showing positive antibody titres as well as for symptomatic relatives, even if serologically negative, to confirm the presence of any pathological conditions and reduce the risk of relapses within families.

Antibodies, Anti-Idiotypic↗

Requesting consent for an invasive procedure in newly deceased adults.

OBJECTIVE: Ethical concerns exist over the performance of medical procedures, such as endotracheal intubation, on newly deceased patients without family consent. This study examined the process of obtaining consent for the purpose of performing an invasive procedure in newly deceased adults. DESIGN: A prospective case series. PARTICIPANTS: The families of patients who died during a 5-month period were requested to provide consent to perform wire-guided retrograde tracheal intubation. MAIN OUTCOME MEASURES: Differences between success and failure in obtaining consent including information on the decreased, family reasons for their decision, and the experience of those requesting consent. RESULTS: Consent was requested from 44 families and 26 (59%) agreed to the procedure. This success rate was achieved despite the lack of a prior relationship with the family by the persons requesting consent. Consent was obtained more frequently in unexpected than expected deaths (77% vs 41%, P = .03). There were no differences in success rates for consent for age, race, sex, or do-not-resuscitate status of the deceased. Spouses consented more frequently than children (77% vs 50%, P = .25). The two physicians reported greater comfort in requesting consent than the nurse anesthetist investigator. In one instance, the consent process may have increased the emotional distress of the family. CONCLUSION: Consent can frequently be obtained from families for an invasive procedure in newly deceased adults. Physicians should reconsider the practice of performing postmortem procedures without obtaining family consent.

Adult↗

Regional distribution of epidermal growth factor, testosterone and dihydrotestosterone in benign prostatic hyperplasia tissue.

In benign prostatic hyperplasia (BPH), basic fibroblast growth factor (bFGF) is found to have a regional distribution, with concentrations in the periurethral zone (where the primitive fibrostromal nodule originates) higher than those of the peripheral subcapsular zone. The aim of the present investigation was to verify whether androgens and epidermal growth factor (EGF) are uniformly distributed from the periurethral to the peripheral zone or whether they show regional differences. Tissue samples, removed by transvesical resection from nine untreated BPH patients, sectioned in periurethral, subcapsular, and intermediate zones, were examined. In the periurethral zone, dihydrotestosterone (DHT), testosterone, and EGF, determined by radioimmunoassay (RIA) techniques after purification on Celite microcolumns and Sep-pak C18 cartridge, showed values significantly higher (mean +/- SD: 1121 +/- 482 pg, 250 +/- 129 pg, and 6.89 +/- 3.28 ng/mg DNA, respectively; P < 0.01) than those of the subcapsular zone (489 +/- 190 pg, 114 +/- 70 pg, and 3.40 +/- 1.90 ng/mg DNA, respectively). A positive linear correlation between EGF, testosterone, and DHT was also observed. The regional distribution of EGF, testosterone, and DHT was similar to that found for bFGF: the highest levels of these factors in the periurethral region allow us to hypothesize on their possible involvement in the rewakening of mesenchymal tissue, leading to the formation of the primitive fibrostromal nodule and then to BPH development.

Data Interpretation, Statistical↗

An "occupational miliary" due to nitrous gases.

The authors report the case of a patient suffering from chemical pneumonia due to nitrous gases of occupational origin which was mistakenly taken for military tuberculosis. Anamnestic, clinical and anatomopathological aspects of this disease, which successively analysed, often make the diagnosis difficult due to their complexity and lack of specificity.

Adult↗

Nutritional epidemiology during school age.

Nutritional research covers different fields, two of which are of particular interest: evaluation of the nutritional status, and epidemiology of food consumption. For many years, studies in these fields have been promoted by our research group, which bases its methodology on anthropometric measurements, bioelectrical impedance measurements, and check of nutritional habits. Our studies involve more than 2500 subjects from pre-school age to adolescence. This work represents the basis for an educational approach with the ultimate aim of improving life styles. One of our first studies on school meals during nursery period and composition and application of "dietary tables" showed inadequacies of energy intakes and macronutrients distribution. In another study, aimed to evaluate the intake of soluble sugars, more than 2/3 of participating school children were found to consume more than 70 g of soluble sugars per day, while 10% of them exceeded 150 g/day. Results of the following study, in which special attention was given to salted and sweet snacks, showed that snacks can account for 34% of the total daily energy intake; although its adequacy, the energy distribution per macronutrients showed a clear imbalance. As for adolescence, a very critical age, the evaluation of weight self-perception revealed that only 62% of them had a correct perception of their weight. This research also devoted special attention to home prepared breakfast, which is consumed by the vast majority of enrolled subjects, although only rarely it is nutritionally adequate. A double age-related trend could thus be drawn: on one side, there is the tendency of the "overweight status" to decrease (from a starting-point of about 20%); on the other side, this tendency is unfortunately compensated by the increasing trend of "obesity" (which almost reaches 30%).

Adolescent↗

[High incidence of Helicobacter pylori infections in an endoscopic pediatric patient series].

We evaluated in children with abdominal complaints the prevalence of Helicobacter pylori gastric and duodenal colonization and the histological features of gastric and duodenal mucosae. Fifty patients, aged 1-17 years, underwent upper endoscopy for recurrent abdominal pain, vomiting and/or gastrointestinal bleeding. With serological, bacteriological and/or histological methods twenty-eight children were demonstrated to be Helicobacter pylori-positive. No statistically significant differences were observed with regard to age, sex and indication to perform endoscopy. Eighty-two percent of Helicobacter pylori-positive patients had gastritis and/or duodenitis. The Helicobacter pylori-positive children had higher Helicobacter pylori specific IgG levels than the Helicobacter pylori-negative ones (p < 0.001). No statistically significant differences were found between Helicobacter pylori-positive and Helicobacter pylori-negative subjects, for gastrin and pepsinogen I. Since the frequency of Helicobacter pylori infection in children with gastrointestinal complaints is high, in patients undergoing upper endoscopy, the sistematical examination of bioptic samples for bacteriological and histologic procedures is of great importance.

Abdominal Pain↗

Chemistry and structure of a new canal sealer showing a dynamical behaviour.

The complete apical seal without percolation and transit of bacteria and their products along the wall of the endodontic canal is the fundamental condition to obtain a lasting result of a correct endodontic therapy. The aim of this study was to characterize a new formulation cement (PROENDO, VEBAS, Italy) with characteristics totally different from the conventional ones. Finally, we can assert that an alloplastic material like PROENDO, which is the subject of this study, bio-compatible, osteo-inductive, non-toxic, with adhesive capacities, is able to quicken the phenomena of restoration and recovery after an endodontic operation.

Calcium Phosphates↗

Malabsorption of different lactose loads in children with human immunodeficiency virus infection.

Thirty children infected with human immunodeficiency virus (HIV) (18 P1 and 12 P2, according to the classification system of the Centers for Disease Control) and 54 noninfected children were evaluated for lactose malabsorption with use of the hydrogen breath test after different lactose loads. Lactose malabsorption after load of 2 g/kg occurred in 75% of P2, 67% of P1, and in 46% of noninfected children. With a lower lactose load (1 g/kg), the prevalence of malabsorption was significantly higher among P2 children than P1 and noninfected cases. A similar figure was obtained after the lowest load (0.5 g/kg). Infected children with lactose malabsorption were significantly younger than noninfected malabsorbers (mean age +/- SD; 50.3 +/- 22 vs. 63.5 +/- 20.9 months) when the load of 2 g/kg was used. The use of lower lactose loads seems to be helpful in finding the dose that can be tolerated. This finding could have nutritional importance and could lead to better dietary management.

Breath Tests↗