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Biomedical subjects

G Brambilla

Publications and source records attributed to G Brambilla.

At least 235 records · Page 13Linked to original sources
PubMedDate not supplied

In vitro toxicity and formation of early conjugates in Caco-2 cell line treated with clenbuterol, salbutamol and isoxsuprine.

Caco-2, human intestinal cell line able to differentiate in long-term culture, has been used to assess the cytotoxicity of the beta-agonists clenbuterol, salbutamol and isoxsuprine, also used at high doses to obtain lean meat in food producing animals, and to investigate the eventual in vitro formation of early conjugates of these compounds. For this purpose, the cells have been characterized for the activity of UDP-glucuronyltransferase, which is present and increases in the differentiated cells, and for the beta-receptors' binding characteristics, which are those of beta 1 and beta 2 subtypes. Isoxsuprine was shown to be the most toxic, followed by clenbuterol and salbutamol. Conjugates have been observed after incubation of the cells both with the lowest isoxsuprine and the highest salbutamol concentrations. No conjugates were detected in the case of clenbuterol.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Cytotoxicity, DNA fragmentation and sister-chromatid exchange in Chinese hamster ovary cells exposed to the lipid peroxidation product 4-hydroxynonenal and homologous aldehydes.

The cytotoxic and genotoxic activities of 4-hydroxypentenal (HPE), 4-hydroxyhexenal (HHE), 4-hydroxyoctenal (HOE), 4-hydroxynonenal (HNE) and 4-hydroxyundecenal (HUE) were investigated in Chinese hamster ovary (CHO) cells. All five 4-hydroxyalkenals reduced plating efficiency in a concentration (ranging from 7 to 170 microM) lower than that producing a parallel reduction of trypan blue-excluding cells, but with both methods the increase in molarity needed to obtain a lethal effect was constantly rather small. With all five 4-hydroxyalkenals a significant amount of DNA fragmentation, as revealed either by the alkaline elution assay or by alkaline denaturation followed by chromatographic partition of single- and double-stranded DNA, was detected only after cell exposure to a cytotoxic concentration. HPE, HHE and HOE induced a clear-cut increase of sister-chromatid exchange (SCE) frequency, while that displayed by cells treated with HNE and HUE was minimal, even if dose-dependent and statistically significant. Since 4-hydroxyalkenals have been shown to originate from biomembrane lipids peroxidation, these findings should be taken into consideration in the assessment of the genotoxic role of lipoperoxidation in humans.

Aldehydes↗
PubMedDate not supplied

Human hepatocytes in genotoxicity assays.

Human hepatocyte primary cultures, because of their comprehensive biotransformation capability, represent an experimental model particularly useful to gain direct information on the genotoxic risk of chemicals to humans. For this purpose they have been used in the last few years either as target cells to evaluate the induction of DNA damage and/or DNA repair synthesis, or as metabolic activation system in mutagenicity assays. The number of compounds so far tested is rather limited, and for the large majority of them the assays have been performed only on hepatocytes from a few donors. A comparison with the data obtained in rat hepatocytes indicates that quantitative differences in the genotoxic effects induced in cultures derived from different donors of the same species are usually greater than interspecies differences. However, the results.provided by some chemicals suggest the possibility that in certain cases rat hepatocytes might be inappropriate predictors of the genotoxic hazard for humans.

Animals↗
PubMedDate not supplied

Change in major amputation rate in a center dedicated to diabetic foot care during the 1980s: prognostic determinants for major amputation.

From 1990 to 1993, 115 diabetic patients were consecutively hospitalized in our diabetologic unit for foot ulcer and 27 (23.5%) major amputations were carried out. The major amputation rate of this series of cases was compared with that occurring in diabetic subjects taken into our hospital for foot ulcer in two previous periods: 1979-1981 (17 major amputations in 42 inpatients or 40.5%) and 1986-1989 (26 major amputations in 78 inpatients or 33.3%). The comparison shows a progressive reduction in major amputation rate [Odds ratio 0.66, 95% confidence interval (CI) 0.46-0.96]. Univariate and multivariate analysis, carried out in the population of the 1990-1993 period, in order to detect the independent factors associated with major amputation show the following prognostic determinants of major amputation: Wagner grade (odds ratio 7.69, CI 1.58-37.53), prior stroke (odds ratio 35.05, CI 3.14-390.53), prior major amputation (odds ratio 3.49, CI 1.26-9.38), transcutaneous oxygen level (odds ratio 1.06, CI 1.01-1.12), and ankle-brachial blood pressure index (odds ratio 4.35, CI 1.58-12.05), while an independent protective role was attributed to hyperbaric oxygen treatment (odds ratio 0.15, CI 0.03-0.64). In accordance with other studies, we, therefore, conclude that a comprehensive protocol as well as a multidisciplinary approach in a dedicated center can assure a decrease in major amputation rate. The parameters of limb perfusion were the modifiable prognostic determinants most strongly predictive for amputation.

Amputation, Surgical↗
PubMedDate not supplied

Relay activity of 17-beta oestradiol and diethylstilbestrol in a mouse-rat system.

The biological activities of diethylstibestrol (DES) of 17 beta-oestradiol (17 beta E) were initially tested, based on the uterus enlargement induced by different doses given with food to immature female mice. In a second series of experiments, the drugs were given in higher doses per os to rats (relay animals) and after 24 h, the livers of the relay rats were removed. Parts of the livers were freeze-dried and were added (10% w/w) to the food of immature female mice, while the remainder underwent chemical analysis to determine the DES and 17 beta E content. When given directly to mice with their food, DES showed about six times more biological activity than 17 beta E. When given through the livers of relay rats, the biological activity of the livers from DES-and 17 beta E-treated relay rats was of the same magnitude. The content of 17 beta E in the livers of relay rats was 10-20 times higher than the DES. Such concentrations corresponded directly to the biological activity of livers. These data show that the bioavailability and the relative potency of xenobiotic drugs and natural hormones may be profoundly altered after passing through metabolic pathways, and may give useful indications for the evaluation of biological activity of residues and contaminants and their metabolites in the food.

Animals↗
PubMedDate not supplied

A randomized trial of aspirin and sulfinpyrazone in patients with TIA.

In a double-blind multicenter study, 124 patients with transient ischemic attacks were randomly allocated to one of two groups treated with aspirin (ASA) or sulfinpyrazone respectively. Patients were followed up to assess the relative efficacy of the two treatments in the prevention of the outcomes of stroke, myocardial infarction, vascular death, and worsening or no improvement of TIAs. No significant difference was observed between the two treatments at the end of the follow-up period. Statistical analysis revealed a significant interaction of sex, treatment, and occurrence of events. Analysis of the results according to sex showed that male patients treated with ASA had a highly significant benefit (p less than 0.001) with a 53% risk reduction for further events. In female patients, sulfinpyrazone showed a favorable trend which was not statistically significant.

Adult↗
PubMedDate not supplied

[An effective immunodepressive treatment for demonstrating in allogeneic mice the tumorigenic properties of cells grown in vitro (author's transl)].

Short intensive treatment with N-diazoacetylglycine amide (DGA) before the inoculum, followed by prolonged daily administration of L-asparaginase (Asnase), was tested for its ability to elicit tumorigenic properties of fibroblast-like cells cultured in vitro. With this treatment progressive tumor growth was obtained in allogeneic mice injected with cells of a transformed subline. Results show that combined use of DGA and Asnase affords a higher probability of proving in vivo the tumorigenic properties of injected cells than in newborm or X-irradiated recipients. Experimental data indicate that L-asparagine depletion does not inhibit the in vitro growth of fibroblast-like cells.

Animals↗
PubMedDate not supplied

[Effects of the cobalt ion on the in vitro growth of mouse fetus fibroblasts (author's transl)].

The effect of cobalt II (CoCl2.6 H2O) on growth and plating efficiency of an established line of BALB/c mouse embryo cells was examined. The degree of inhibition of cell proliferation was dependent on both cobaltous ion dose and duration of treatment. Plating efficiency was enhanced by low doses and/or short time of exposure, but was reduced by treatment with higher doses or of longer duration.

Animals↗
PubMedDate not supplied

Direct interaction with cellular targets as the mechanism for chromium carcinogenesis.

The carcinogenic activity of chromium appears to be due to its direct interaction with cellular targets and not to nonspecific solid-state carcinogenesis. Chromium was evaluated at 2 valences, Cr+3 (as CrC13) and Cr+6 (as K2Cr2O7), for its toxicity, transforming activity, and ability to induce chromosomal aberrations in tertiary cultures of mouse fetal cells. The ID50 (dose for 50 percent inhibition of cell growth) of Cr+3 was approximately 4 times greater than that of Cr+6 after 96 h of exposure, and about 29 times greater than that of Cr+6 after 1 h of exposure. At equitoxic concentrations, both chromium valences induced the same degree of morphologic changes and alterations of growth behavior, but Cr+6 produced more chromosomal aberrations. Using autoradiography in an established cloned line of mouse cells, unscheduled DNA synthesis was observed in cells previously exposed to Cr+6 but not in cells previously exposed to Cr+3.

Animals↗
PubMedDate not supplied

Cisplatin, mitomycin-C, 5-fluorouracil and leucovorin combination chemotherapy (l-FCM) in locally advanced unresectable or metastatic gastric carcinoma: a phase-II study.

Despite relevant progress, the impact of chemotherapy on advanced gastric cancer patients' survival is still unsatisfactory. Thus, the key objective of our efforts should be palliation of the symptoms and the maintenance of an adequate quality of life. In this phase-II study, we evaluated toxicity and efficacy of the combination of cisplatin, fluorofolates and mitomycin C. Thirty-one advanced gastric cancer patients received cisplatin (15 mg/m2) and 5-fluorouracil (350 mg/m2), both for 5 consecutive days every 4 weeks; 5-fluorouracil infusion was preceded by a rapid i.v. injection of 100 mg/m2 leucovorin, while mitomycin-C (10 mg/m2) was administered on day 1 of odd cycles. Cycles were repeated every 4 weeks until disease progression. We recorded 16 objective responses (51.6%, 95% confidence interval: 42.63-60.57); furthermore, such a response rate was coupled with a moderate degree of toxicity and an extremely good tolerance. In particular, alopecia, a frequent and distressing side-effect in patients, especially women, in our series occurred only in two patients. This treatment appears to be an active and tolerable therapeutic option for patients with advanced gastric carcinoma.

Adult↗
PubMedDate not supplied

Therapy for recurrent acute pericarditis: a rheumatological solution?

OBJECTIVE: To assess the efficacy of a multidrug protocol in recurrent acute pericarditis. We tried also to assess the specific role of colchicine. METHODS: We studied 58 patients (34 males) in the largest monocentric observational study. All patients received prolonged courses of non-steroidal anti-inflammatory drugs; generally we do not start a corticosteroid in recurrent acute pericarditis, but if a steroid had already been started, we planned a very slow tapering; if necessary azathioprine, hydroxychloroquine, and other immunosuppressive drugs were used; 44 patients (27 males, 61.4%) were treated also with colchicine and 14 patients (7 males, 50%) were not given this drug. RESULTS: After starting our protocol recurrences dropped from 0.48 to 0.03 attacks/patient/month (p < 0.00001) within 12 months and remained at the same level till the end of the follow-up (mean 8.1 years) in the whole cohort. In the 44 patients treated with colchicine recurrences dropped from 0.54 to 0.03 attacks/patient/month (p < 0.00001) within 12 months, and in 14 patients not given colchicine recurrences decreased from 0.31 to 0.06 attacks/patient/month (p = 0.002). In patients treated with colchicine the decrease was significantly higher (0.51) than in patients not taking this drug (0.25) (p = 0.006). Colchicine was discontinued by 16.3% of patients because of side effects. CONCLUSION: A multidrug protocol including non-steroidal anti-inflammatory drugs at high dosage, slow tapering of corticosteroid, colchicine, reassurance and close clinical monitoring is very effective in recurrent pericarditis; this improvement is more dramatic in colchicine treated patients, but also patients who do not tolerate it can achieve good control of the disease.

Acute Disease↗
PubMedDate not supplied

[Sepsis, acute renal failure and multiple organ dysfunction syndrome].

The so-called systemic inflammatory response syndrome (SIRS ) represents the cellular inflammatory and neuroendocrine systemic reaction in response to many adverse events. epsis is defined as IR induced by bacterial, mycotic or viral toxins. The circulating toxins deriving from the bacterial wall can activate the septic cascade that induces many systemic reactions involving the activation of the cellular immunity, complement and coagulation system. The endothelial cell is the target of the systemic phlogistic reaction; its stimulation is followed by the production of many vasoactive paracrine and systemic agents. In this context, local and systemic cytokine production plays a major role in inducing the septic cascade, which although meant to be a phlogistic defense reaction, can often become an uncontrolled and dangerous inflammatory reaction. The sepsis-derived lesions can involve many organs and apparatus leading to the picture of sepsis syndrome. Sepsis syndrome often induces severe pulmonary lesions with a picture of acute respiratory distress syndrome (ARDS ). The combination of acute renal failure and sepsis is associated with a high mortality rate, namely in patients with a nitric oxide-induced systemic reduction in peripheral vascular resistances and septic shock. The toxinemia can also induce myocardial damage with a reduction in cardiac performance. Therefore, septic patients who have a combination of pulmonary, cardio-vascular, renal and cerebral lesions present with the picture of multiple organ dysfunction syndrome, that can increase mor-tality to > 0%.

Acute Kidney Injury↗