Biomedical subjects

F Feo

Publications and source records attributed to F Feo.

114 records · Page 7Linked to original sources

PubMedDate not supplied

Genomic abnormalities in hepatocarcinogenesis. Implications for a chemopreventive strategy.

Carcinogenesis is a complex process characterized by the cumulative activation of various oncogenes and the inactivation of suppressor genes. Epigenetic mechanisms are also involved. Mutational activation of ras family genes occurs in most spontaneous or carcinogen-induced liver tumors, in susceptible mice, and less frequently in preneoplastic lesions. This suggests a pathogenetic role of these changes in hepatic carcinogenesis, in the mouse. Overexpression of various growth-related genes occurs in preneoplastic tissue during rat liver carcinogenesis, but mutational activation of protooncogenes, notably of ras family genes, seems to be a late and rare event, while c-myc amplification is a late but frequent event in both rodent and human carcinogenesis. However, mutation of the suppressor p53 gene has been found in relatively early preneoplastic lesions in rat liver, and it may be frequently seen in human hepatocellular carcinomas. The possibility that this mutation is involved in the initiation stage of liver carcinogenesis is an attractive hypothesis which needs further evaluation. DNA hypomethylation is involved in carcinogenesis, but the mechanisms underlying this effect are still elusive. Hypomethylation of growth-related genes is associated with their overexpression and this could favor overgrowth of preneoplastic liver tissue. Decrease in S-adenosyl methionine/S-adenosylhomocysteine (SAM/SAH) ratio occurs in the liver of rats fed a methyl deficient diet, which is a carcinogenic treatment, and in preneoplastic liver tissue, developing in initiated/promoted rats fed an adequate diet. The role of low SAM/SAH ratio in carcinogenesis is substantiated by the tumor chemopreventive effect of lipotropic compounds. Treatment with exogenous SAM prevents the development of preneoplastic and neoplastic lesions in rat liver. This is associated with recovery of SAM/SAH ratio, DNA methylation and inhibition of growth-related gene expression. SAM effect on prenoplastic cell growth is abolished by 5-azacytidine, a hypomethylating agent, indicating the involvement of DNA methylation. The possibility that in SAM-treated rats, methylation and inhibition of the expression of growth-related genes is implicated in growth restraint is attractive and should be further evaluated. Modulation of rat liver carcinogenesis by influencing gene expression through DNA methylation or other epigenetic mechanisms could be a new approach to chemoprevention of these tumors.

Adenoma↗

PubMedDate not supplied

Effect of S-adenosyl-L-methionine on the development of preneoplastic foci and the activity of some carbohydrate metabolizing enzymes in the liver, during experimental hepatocarcinogenesis.

gamma-Glutamyltranspeptidase (GGT)-positive foci and glutathione-S-transferase, placental (GST-P)-positive lesions occupied 36% and 54% of liver parenchyma, respectively, in Wistar rats 8 weeks after initiation with diethylnitrosamine, followed by selection. The administration of S-adenosyl-L-methionine (SAM, 384 mumol/kg/day) caused 77% and 42% falls in the percentage of GGT-positive and GST-P-positive lesions, respectively. There also occurred a 46% decrease in labeling index of GGT-positive foci, in SAM-treated rats. These changes were associated with decrease in liver pyruvate kinase (PK), lactate dehydrogenase and glycerol-3-phosphate dehydrogenase. SAM did not affect these enzymatic activities in normal and uninitiated controls, but it caused a consistent increase in initiated rats. Enolase, fructose-biphosphatase and malic enzyme (ME) activities increased in the liver of initiated rats. SAM did not modify significantly these enzymatic activities, either in control or in initiated rats. Glucose-6-phosphate dehydrogenase (G6PDH) was 113% higher in the liver of initiated rats than in uninitiated controls. SAM treatment did not significantly affect this enzymatic activity in uninitiated rats, but caused a great decrease in initiated ones. As expected, there occurred a marked rise in GGT activity in the liver of initiated rats, with respect to controls. SAM caused an increase in GGT activity in normal and uninitiated controls, but it caused a 77% fall in GGT activity in initiated rats, coupled with a 380% rise in remodeling of GGT-positive lesions. Histochemical determination of G6PDH and ME activities showed that in the absence of SAM many preneoplastic lesions expressed higher G6PDH and ME activities than surrounding liver. SAM did not affect ME-positive lesions, while it caused a decrease in the number of G6PDH-positive lesions. Immunohistochemical determination of PK activity, isoenzyme L, showed a decrease in GST-P-positive lesions. Many of these lesions were no longer recognizable as lesions expressing a low PK activity, in SAM-treated rats. However, a relatively small number of GST-P-positive lesions expressing a low PK activity were still present in these rats. These data suggest that glucose channelled into triacylglycerol and pyruvate synthesis decreases in rat liver, during the development of preneoplastic foci, while the production of reducing equivalents and pentose phosphates increases, thus favoring DNA synthesis and detoxification reactions. Decrease in DNA synthesis, in SAM-treated rats, is paralleled by a partial reversion of carbohydrate metabolic features to those present in normal liver.

Animals↗

PubMedDate not supplied

[Investigation of the efficacy and tolerability of azelastine nasal spray versus ebastine tablets in patients with seasonal allergic rhinitis].

The efficacy and safety of the nasally administered histamine H1 receptor blocking drug Azelastine was investigated in an open, multicenter, randomized comparative trial with Ebastine in seasonal allergic rhinitis. 110 patients in two parallel groups were treated for 14 days and efficacy was assessed by the physician using a rating scale measuring 10 nasal and ocular symptoms of seasonal rhinitis (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Tolerability was measured on the basis of reported adverse events. Both treatment groups had dramatic reductions in the physician's total symptom score following treatment (p < 0.0005). There was no significant difference between the two groups. Changes in individual rhinitis symptoms showed no differences between the two groups. During treatment, 19 patients had at least one adverse event, 13 in Azelastine group and 6 in Ebastine group; all were mild. The most frequent adverse events reported were somnolence (4 cases in Ebastine group) and a bitter taste (4 patients in the Azelastine group). In conclusion, the results of the study on 110 patients suggest that both Azelastine and Ebastine are effective treatments of the symptoms of seasonal allergic rhinitis. Both drugs were well tolerated.

Administration, Intranasal↗

PubMedDate not supplied

Hypersensitivity to chironomid larvae.

Chironomid larvae (red midge larvae) are often used by aquarists as fish food. Their hemoglobins can cause IgE-mediated allergic diseases in exposed and unexposed people. The aim of this study was to find out the prevalence of positive skin tests to chironomids in patients suffering from rhinitis and/or bronchial asthma in Ciudad Real (Spain). A total of 465 patients were submitted to skin prick tests with chironomids in addition to common inhalant allergens. The patients with positive skin prick test (wheal > or = 3 mm) to these larvae answered a questionnaire. Skin prick tests with Acarus siro, shrimp, cockroach and mosquito (Culex pipiens) were carried out. Serum levels of total IgE and anti-Chironommus thummi, anti-Dermatophagoides pteronyssinus, anti-shrimp, and anti-mosquito (Aedes communis) IgE were determined. Conjunctival or nasal provocation tests were carried out with chironomids. Of the 465 patients skin tested, 19 showed a positive skin prick test with chironomids, corresponding to 4.1% of all patients and 6% of the atopic patients. None were monosensitized. Significant correlations were found between skin prick test results with chironomids and mites (p < 0.005). Of the 19 patients, 15 had positive skin prick test with the common mosquito C. pipiens. Seven patients showed elevated anti-D. pteronyssinus IgE, six elevated anti-shrimp IgE, and 10 showed elevated anti-A. communis IgE. Provocation tests with chironomids were positive in 14 patients (four nasal and 10 conjunctival tests). Conjunctival provocation tests were carried out in 16 controls and were positive in three; all three showed positive skin prick test with chironomids. One patient had occupational allergy from the larvae (aquarist). After mosquito bites, five patients showed immediate wheal reactions and one patient suffered an anaphylactic reaction after several mosquito bites. Only two patients remembered having been in contact with chironomids as fish food. We found hypersensitivity to these larvae in patients without apparent contact to them. These patients could have become sensitized in various ways, including: 1) inhaling particles of chironomids or others that are cross-reactive with them; 2) exposure to products used as fish food containing chironomids; and, 3) through cross-reactivity with other allergens such as mites, shrimp or mosquitoes.

Adolescent↗

PubMedDate not supplied

Anaphylaxis to paracetamol.

We hereby present a patient suffering several episodes of anaphylaxis (generalized urticaria, dyspnea, wheezing and intense cough) a few minutes after taking different drugs containing paracetamol. Intradermal test with pure paracetamol (100 mg/ml) was positive. It was negative in six controls. Serum specific IgE anti-paracetamol (by RIA) was negative. Anaphylaxis from paracetamol is rare but has been reported. Positive skin test with paracetamol have only been rarely described.

Acetaminophen↗

PubMedDate not supplied

Mosquito bite hypersensitivity.

We report a patient who experienced systemic anaphylaxis after several mosquito bites. The skin tests were positive, by prick and intradermal tests, with two species of common mosquito (Aedes communis and Culex pipiens) and also with red midge larvae (Chironomus). Specific IgE against Aedes communis was demonstrated. We carried out SDS-PAGE and immunoblotting with whole body extracts of Aedes communis and Culex pipiens and with red midge larvae. The immunoblotting results showed specific IgE against two proteins of approximately 30 kDa with the extract of Culex pipiens. We also found IgE against one protein of a slightly lower molecular weight with Aedes communis, and against several proteins (the most important with a molecular weight between 30 and 70 kDa) with the Chironomus extract. Cross-reactivity between these insect species was suspected.

Adult↗