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G Brambilla

Publications and source records attributed to G Brambilla.

At least 55 records · Page 3Linked to original sources
PubMed1998

Increased frequency of micronucleated kidney cells in rats exposed to halogenated anaesthetics.

Six halogenated anaesthetics were tested for their ability to induce micronuclei formation in the rat kidney. A statistically significant increase in the frequency of micronucleated cells was detected in rats given a single p.o. dose of 4 mmol/kg of halothane (3.48 x baseline), chloroform (3.32 x baseline), trichloroethylene (3.24 x baseline), sevoflurane (2.98 x baseline), and isoflurane (2.95 x baseline). In contrast, the response was substantially negative in rats given the same dose of enflurane. As compared to controls, rats treated with halothane and trichloroethylene displayed a reduction in the frequency of binucleated cells presumably due to a toxicity-induced inhibition of cellular proliferation. These findings suggest a potential genotoxic activity of halogenated anaesthetics for the rat kidney.

Anesthetics, Inhalation↗
PubMed1998

Characterization of furazolidone apical-related effects to human polarized intestinal cells.

In studying the effects of furazolidone (FZ) on the human intestinal Caco-2 cell line grown on microporous membrane, we have previously demonstrated a higher toxicity when the compound was administered at the apical (AP) side than at the basolateral (BL) side. Moreover, we have also shown the production, in the intact cells, of a nitroanion radical from FZ by a cytochrome c P450 reductase. The aim of the present study was to investigate which specific cell structures and functions are involved in the observed domain-related toxicity. The relevance of alterations in integrity and selective properties of the intestinal barrier as first-pass site for ingested molecules is also discussed. We have confirmed that, as expected, the Caco-2 cells are protected from FZ injury by a specific inhibitor of the cytochrome c P450 reductase, and we have shown that this protection is more active on the apical side of the cells. In sublethal conditions, FZ causes increased permeability to 3H-mannitol and, to a different extent, to 3H-inulin. Again the effect is higher when the cells are apically exposed. We have thus examined the tight junctions morphology: a disruption of the apical perijunctional actin-bound cytoskeleton was detected by rhodamine-phalloidin staining and microtubule disorganization by antitubulin fluoresceinated antibodies. Again, the effect was more evident when the cells were apically treated with FZ. Preferential transport and accumulation of the compound by active transport mechanisms could be excluded, since transport of FZ was linear and no intracellular accumulation was detected either from the AP and or the BL sides. All together these results may suggest that the AP formation of the active metabolite and its possible reactivity with SH groups of perijunctional microfilaments could be responsible of the higher FZ apical toxicity. This study shows that polarized differentiated cells are very interesting in vitro models to investigate specific cellular domains as targets of toxic effects and to detect subtle changes that may be induced, in absence of cell death, in specialized epithelial layers.

Actin Cytoskeleton↗
PubMed1998

A possible correlation between the blood leukocyte formula and the use of glucocorticoids as growth promoters in beef cattle.

Clinical analyses designed to set welfare parameters were performed on blood drawn from the caudal vein of 14 groups of cattle (young bulls and heifers) (n = 10) from 480 to 550 kg b.w., each group representative of a different farm. The leukocyte formula exhibited a lymphocytopenia in four groups compared with the values from a control group (n = 50). This finding was related to the possible illicit use of corticoids as growth promoters in meat production. The individual plasmas tested negative by two different ELISA kits for corticosteroids, but chemical analyses by LC-MS/APCI (detection limit 0.5 ng/ml) on the pooled plasma of each of the 14 groups revealed the presence of beclomethasone and fluocinolone acetonide in 3 of the 4 suspect farms. These corticosteroids are not always efficiently screened by commercially available immunoassays. The epidemiological reliability of blood analysis as a screening test for such drugs is discussed in the light of the need for quality certification of the whole meat production processes 'from farm to fork', and for enhanced animal welfare.

Animals↗
PubMed1998

Alpha 1-acid glycoprotein affinity columns for the clean-up of adrenergic drugs.

alpha 1-Acid glycoproteins (AAGs) have a structure resembling beta-adrenergic receptors and bind several basic drugs in plasma. Chromatographic columns were prepared by linking epsilon-NH2 groups of AAG lysines to a Sepharose 4B support, in order to purify by affinity chromatography adrenergic drugs of possible use in animal production. Loading capacities, binding efficiency, memory effects and matrix interferences from urine samples were studied. The method developed involves sample application in buffered media (pH 7.4), washing with 5 ml of PBS, and elution with 4 ml of 1% v/v acetic acid. Under these conditions no memory effect was observed. Loading capacity is correlated with the physiological plasma binding rate (PB) of the drug. For clenbuterol (PB 50%) and anilino-like related drugs, 5 mg of AAG were able to bind about 15 x 10(-6) g of drug, with a 100% recovery from the column. Repeatability and reproducibility, expressed as RSD, were 4.2 and 5.4%, respectively. The calculated AAG: drug molar ratio was 4.5:1, indicating 22% of the AAG bound to the column retained drug affinity. Among phenolic-like agonists, salbutamol (PB 5%), fenoterol and isoxsuprine hardly interacted, whereas nylidrin, ritodrine and bamethan showed more effective binding. We also checked binding of other drugs of possible use in veterinary medicine. Application of the AAG column to spiked bovine urine revealed a mean recovery of 97.8%; no matrix interferences were observed.

Adrenergic beta-Agonists↗
PubMed1998

The Seveso studies on early and long-term effects of dioxin exposure: a review.

The industrial accident that occurred in the town of Seveso, Italy, in 1976 exposed a large population to substantial amounts of relatively pure 2,3,7,8-tetrachlorodibenzo-p-dioxin. Extensive monitoring of soil levels and measurements of a limited number of human blood samples allowed classification of the exposed population into three categories, A (highest exposure), B (median exposure), and R (lowest exposure). Early health investigations including liver function, immune function, neurologic impairment, and reproductive effects yielded inconclusive results. Chloracne (nearly 200 cases with a definite exposure dependence) was the only effect established with certainty. Long-term studies were conducted using the large population living in the surrounding noncontaminated territory as reference. An excess mortality from cardiovascular and respiratory diseases was uncovered, possibly related to the psychosocial consequences of the accident in addition to the chemical contamination. An excess of diabetes cases was also found. Results of cancer incidence and mortality follow-up showed an increased occurrence of cancer of the gastrointestinal sites and of the lymphatic and hematopoietic tissue. Experimental and epidemiologic data as well as mechanistic knowledge support the hypothesis that the observed cancer excesses are associated with dioxin exposure. Results cannot be viewed as conclusive. The study is continuing in an attempt to overcome the existing limitations (few individual exposure data, short latency period, and small population size for certain cancer types) and to explore new research paths (e.g., differences in individual susceptibility).

Adolescent↗
PubMed1998

Angiographic evaluation of peripheral arterial occlusive disease and its role as a prognostic determinant for major amputation in diabetic subjects with foot ulcers.

OBJECTIVE: To evaluate in diabetic patients with foot ulcers the angiographic findings of peripheral occlusive arterial disease and their role as a prognostic determinant for major amputation. RESEARCH DESIGN AND METHODS: From 1993 to 1995, 104 diabetic inpatients with foot ulcers underwent arteriography on the ulcerated limb. Stenoses in the iliac trunk, the superficial femoral artery, the profunda femoral artery, the popliteal artery, the anterior tibial artery, the posterior tibial artery, and the peroneal artery were scored on the basis of vessel lumen reduction: 0 if stenoses involved a reduction in the vessel lumen of < 50%, 1 if stenoses involved 50 to < 75% reduction, 2 if stenoses involved 75 to < 100% reduction, and 3 if total occlusion was present. The sum of the points assigned to each of these arteries was called the angiographic score. RESULTS: Stenoses causing a vessel lumen reduction > or = 50% were detected in 103 patients (99%). Stenoses were also detected in subjects with palpable foot pulses, ankle-brachial indexes > or = 1, or transcutaneous oxygen tension > or = 50 mmHg. The risk of major amputation was increased significantly when total occlusion was present in the popliteal and infrapopliteal arteries (chi 2 for trend = 50.57, P < 0.001). No major amputation was carried out in patients with angiographic scores < 10; major amputation was carried out in all the patients with scores > 14. Multivariate analysis indicated a high angiographic score as an independent risk factor for major amputation (odds ratio 2.32, P = 0.001, CI 1.40-3.84). CONCLUSIONS: Angiography permits an exact detection of occlusive arterial disease in subjects with normal results for noninvasive vascular procedures. A score that has a relevant prognostic value for major amputation can be obtained from the evaluation of the extent and diffusion of the stenoses.

Amputation, Surgical↗
PubMed1998

Clenbuterol residues in non-liver containing meat as a cause of collective food poisoning.

beta 2-adrenergic agonists, particularly clenbuterol, are illegally used as growth promoters to obtain lean in meat. Their administration in feedlots can constitute a severe risk for animal welfare and exposes consumers to involuntary drug consumption at pharmacological active concentrations. Reported poisoning episodes have been associated with the consumption of beef liver where clenbuterol residues concentrate. In August 1996, 62 persons asked for medical help at the emergency rooms of 2 hospitals near the city of Caserta (Italy). Their clinical profile was characteristic of previously occurring clenbuterol intoxication, which reported superventricular extrasystoles and atrial fibrillation. All patients had non-liver beef meat consumption 10-30 min to 2-3 h before symptoms developed. An ELISA screening test specific for clenbuterol confirmed the drug's presence. Definitive confirmation of clenbuterol and determination of the drug content in meat samples were obtained by GC-MS, using 2 different derivatization. Concentrations in the meats ranged from 0.8 to 7.4 mg/kg. These analytical data provided evidence of the seriousness of the poisoning and helped the National Health System identify other possible misinterpreted cases. This case demonstrates that clenbuterol poisoning can also occur after consumption of beef meat other than liver.

Adolescent↗
PubMed1998

[Survival of 184 patients with hepatocellular carcinoma in cirrhotic liver treated with chemoembolization. A multicenter study].

INTRODUCTION: We report the results of a multicenter study of 184 cirrhotic patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) and compare our results with those reported in the literature. MATERIAL AND METHODS: We treated 184 cirrhotic FNB-proved HCC patients with TACE in a 2 years' period; 159 were men and 25 women and their mean age was 59 years (range: 46-75 years). TACE was performed with selective or superselective injection of Doxorubicin chlorhydrate (20-50 mg) mixed with Lipiodol Ultrafluid before embolization with Spongostan. This procedure was repeated after 4-6 weeks for at least 3 cycles. Follow-up was performed by means of periodic US, CT and MR scans and by assessment of the clinical status and serum biochemical tests--alpha-fetoprotein, platelet and blood cell counts, protein electrophoresis, bilirubin and other standard liver and renal function tests. TACE results were assessed comparing site, size and local spread of tumor and TACE technique (lobar or segmental, number of performed procedures) with survival in each patient. The lesion was single in 85 (46.2%) and multiple in 99 (53.8%) patients. It exceeded 5 cm in 128 patients (69.5%) and was < 5 cm in 57 (30.5%). RESULTS: Angiography, CT and MRI showed complete necrosis in 148 patients (80.4%) and an unchanged pattern in 36 (19.6%). Overall survival rates were 95.7% at 6 months, 78.3% at 1 year, 46.0% at 2 years, 40.0% at 3 years. The best responses were obtained with lesions < 5 cm--with 100% survival at 6 months, 94.8% at 12 months, 71.4% at 18 months, 54.7% at 24 months and 50.0% at 36 months. Other factors affecting treatment response were singleness of lesion (96.4% at 6 months, 93.9% at 12 months, 71.4% at 18 months, 58.9% at 24 months, and 50.0% at 36 months) and at least 3 cycles of TACE (100% at 6 months, 87.8% at 12 months, 70.1% at 18 months, 48.7% at 24 months and 37.5% at 36 months). Abdominal pain and fever were the most frequent complications, particularly in the first TACE procedure, but both were mild and transient. Lipiodol cholecystitis was found in 3 patients but they were asymptomatic. No patients had evidence of cardiac toxicity or experienced significant leukopenia or thrombocytopenia as a result of systemic toxicity from Doxorubicin. CONCLUSIONS: We can conclude that TACE proves to be an efficacious treatment in the HCC patients who cannot undergo surgery.

Aged↗
PubMed1997

An in vivo micronucleus assay for detecting the clastogenic effect in rat kidney cells.

A micronucleus assay in vivo has been developed that is based on the use of freshly isolated kidney cells from mononephrectomized rats. In this validation study, a statistically significant increase in the frequency of micronucleated cells was detected in rats given i.p. a single dose of four kidney carcinogens, N-nitrosodimethylamine, N-nitrosodiethylamine, N-ethyl-N-hydroxyethylnitrosamine and N-nitroso-N-methylurea. The clastogenic effect was more marked when the same dose was injected for 3 successive days. As compared to controls, treated rats displayed a reduction in the frequency of binucleated cells, presumably due to a toxicity-induced inhibition of cellular proliferation. The proposed method should be suitable for the detection of the clastogenic effect of procarcinogens biotransformed into reactive species in the kidney.

Animals↗
PubMed1996

Evaluation of the potential carcinogenic activity of Senna and Cascara glycosides for the rat colon.

Anthraquinone glycosides of Senna and Cascara were investigated for their ability to induce aberrant crypt foci (ACF) in the rat colon mucosa, which are considered putative preneoplastic lesions. Dietary exposure to high doses of these glycosides for 56 successive days did not cause the appearance of ACF or increase in incidence of ACF induced by 1,2-dimethyl-hydrazine (DMH). However, in rats treated with both DMH and the highest dose of glycosides, the average number of aberrant crypts per focus, considered a consistent predictor of tumor outcome, was higher than in rats given DMH alone. These findings suggest that Senna and Cascara glycoside might behave as weak promoters in rat colon carcinogenesis.

Animals↗
PubMed1996

DNA damage induced by seven N-nitroso compounds in primary cultures of human and rat kidney cells.

Seven N-nitroso compounds (NOC), known to induce kidney tumors in rats, were assayed for DNA-damaging activity in primary cultures of human and rat kidney cells. DNA fragmentation was measured by the alkaline elution technique. Positive responses were obtained in cells of both species with N-nitrosodimethylamine (32 mM), N-nitrosodiethylamine (32 mM), N-nitrosodi-n-propylamine (10 mM), N-ethyl-N-hydroxyethylnitrosamine (18 mM), and streptozotocin (1 mM). N-nitrosodiethanolamine and N-nitrosomorpholine were inactive at the highest concentration tested (32 mM). The responses of human kidney cells were qualitatively similar to those of rat kidney cells, but statistically significant differences between the two species in the DNA-damaging potencies were observed with N-ethyl-N-hydroxyethylnitrosamine and streptozotocin, both more genotoxic in rat cells. Taken as a whole, the results suggest on the one hand that the five active NOC might be carcinogenic for the kidney in humans, and on the other hand that the rat kidney cell/DNA damage assay is a valid model for predicting the genotoxic potential of NOC in human kidney cells.

Animals↗
PubMed1996

Distribution of the anthelmintic drug albendazole and its major metabolites in ovine milk and milk products after a single oral dose.

The distribution of albendazole (ABZ) and its main metabolites albendazole sulphoxide (ABZSO), albendazole sulphone (ABZSO2) and albendazole 2-aminosulphone (NH2ABZSO2) were investigated in bulk milk and milk products after administration of a single oral dose of the drug (12.5 mg/kg) to 80 Laticauda sheep. An analytical method was developed for this investigation from an existing procedure used for the determination of these compounds in plasma and digesta samples. No traces of the parent compound or NH2ABZSO2 were found in milk or milk products, with the exception of the milk collected 36 h after treatment in which 89 micrograms NH2ABZSO2/kg was detected. Results indicated that ABZ was rapidly oxidized to ABZSO and then to ABZSO2. These metabolites were found at high levels (1-4 mg/kg) in milk collected within 24 h after treatment. Products derived from such milk also contained high concentrations of the two oxidized metabolites, including up to 5 mg ABZSO/kg in Pecorino cheese. Only small quantities of these two metabolites were found in milk collected during the second day after treatment (range 50-500 micrograms/kg). They were no longer detectable in milk collected during the third day after dosing, nor were they found in products made from such milk. These findings confirm that the two polar metabolites ABZSO and ABZSO2 were efficiently excreted from the body. Considering that the established maximum residue limit for ovine milk is 100 micrograms/kg for ABZ plus its metabolites, our results confirmed the appropriateness of the currently prescribed withdrawal time (3 d) after the use of ABZ in lactating sheep. However, considerable levels of ABZSO were detected in milk collected within 24 h after treatment as well as in products and by-products derived from such milk. Owing to the known toxicity of the ABZSO, we stress the need for careful control to ensure adherence to the prescribed withdrawal time.

Albendazole↗
PubMed1996

Induction of micronuclei and initiation of enzyme-altered foci in the liver of female rats treated with cyproterone acetate, chlormadinone acetate, or megestrol acetate.

The synthetic anti-androgen and progestin cyproterone acetate (CPA), recently found to be genotoxic for the liver, and two structurally similar progestins, chlormadinone acetate (CMA) and megestrol acetate (MGA), have been compared for clastogenic and tumor-initiating activities in female rats. In the micronucleus assay, carried out in rats given a single p.o. dose of 100 mg/kg, CPA induced the maximum increase in the frequency of micronucleated hepatocytes (6.6-fold as compared to controls) when treatment was performed 3 days before partial hepatectomy and cell sampling 2 days later. Under the same experimental conditions the clastogenic potencies of CMA and MGA were 69% and 36% of that of CPA respectively. In the liver foci assay, p.o. dosing with 100 mg/kg CPA once a week for 6 successive weeks induced, as compared to controls, a significant increase in the number and area of gamma-glutamyltranspeptidase-positive foci. At the same dosage schedule the tumor-initiating activity of CMA and MGA was 7- to 10-fold lower than that of CPA. These findings suggest that the 1,2 alpha-methylene group, present in CPA but absent in both CMA and MGA, favours the activation to a reactive species and/or hinders the biotransformation to non-toxic metabolites.

2-Acetylaminofluorene↗
PubMed1996

Comparative study of DNA repair induced by cyproterone acetate, chlormadinone acetate and megestrol acetate in primary cultures of human and rat hepatocytes.

Cyproterone acetate (CPA), a synthetic progestin recently found to induce genotoxic effects in hepatocytes from female rats and from humans of both genders, and two structural analogues, chlormadinone acetate (CMA) and megestrol acetate (MGA), have been compared for their capacity to induce DNA repair synthesis as measured by quantitative autoradiography. Exposure of primary human hepatocytes for 20 h to concentrations of CPA, CMA and MGA ranging from 2 to 50 microM induced positive responses in cultures from donors of both genders and the amounts of DNA repair elicited by the three progestins were similar. Under the same experimental conditions substantial differences were observed in the amounts of DNA repair elicited by the three progestins in primary hepatocytes from female rats, their potency decreasing in the following order CPA > CMA > MGA, and the three compounds failed to induce DNA repair in hepatocytes from male rats. These results, which agree with previous findings, suggest that for these sex steroids extrapolation to humans of results obtained in rats might be questionable.

Animals↗
PubMed1996

Genotoxic effects of alpha-hexachlorocyclohexane in primary cultures of rodent and human hepatocytes.

The genotoxicity of alpha-hexachlorocyclohexane (alpha-HCH) was evaluated in primary cultures of mouse, rat and human hepatocytes. DNA fragmentation was measured by the alkaline elution technique and DNA repair synthesis by quantitative autoradiography. A 20 h exposure to subtoxic concentrations ranging from 0.056 to 0.32 mM produced a dose-dependent frequency of DNA breaks in rat hepatocytes and in hepatocytes from four of five human donors, but not in mouse hepatocytes, DNA repair induction was absent in hepatocytes from all three species. The reduction in the frequency of DNA breaks observed in rat hepatocytes simultaneously exposed to metyrapone suggests that alpha-HCH is transformed into reactive species by a cytochrome P450-dependent reaction. The detection of DNA fragmentation but not of DNA repair synthesis may be tentatively explained by assuming that alpha-HCH behaves as a chemical eliciting short patch DNA repair, which is more easily revealed as genotoxic by the occurrence of DNA single-strand breaks.

Animals↗
PubMed1996

Feasibility and effectiveness of peripheral percutaneous transluminal balloon angioplasty in diabetic subjects with foot ulcers.

OBJECTIVE: The aim of this study was to evaluate the feasibility and effectiveness of this vascular procedure in diabetic inpatients with foot ulcers. RESEARCH DESIGN AND METHODS: In 80 consecutive inpatient diabetic subjects with a foot ulcer, an angiographic study of the lower limbs was carried out to evaluate the necessity and possibility of performing vascular procedures. In 22 subjects, vascular procedure was not necessary; in 26 subjects, peripheral transluminal angioplasty was carried out; in 10 subjects, angioplasty was considered impossible and a peripheral bypass graft was performed; and in 22 subjects, no vascular procedure was considered possible. RESULTS: Of the 26 angioplasties, 8 were performed in iliac or femoral arteries and 18 were performed in the popliteal artery and its branches. The angioplasty was considered unsuccessful in 4 subjects and successful in 22. After angioplasty, on discharge, parameters of limb perfusion improved significantly: transcutaneous oxygen tension was 27.0 +/- 14 mm/Hg on admission and 44.6 +/- 14 mm/Hg on discharge (P < 0.001); ankle-brachial index was 0.61 +/- 0.23 on admission and 0.77 +/- 0.20 on discharge (P = 0.018). Of 22 subjects who underwent successful angioplasty, 21 ended the follow-up of 12 months: during this period, they showed no relapses in the salvaged limb, and their parameters of limb perfusion did not significantly vary. CONCLUSIONS: Angioplasty is feasible in a large percentage of diabetic subjects with peripheral occlusive arterial disease and foot ulcer and is often also practicable in the popliteal artery and its branches. In these subjects, angioplasty significantly improves the parameters of limb perfusion. Angioplasty is therefore an important therapeutic tool in ulcerated diabetic foot care.

Aged↗