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Biomedical subjects

F Merlo

Publications and source records attributed to F Merlo.

At least 19 recordsLinked to original sources
PubMed2006

Dynamics of the ion cyclotron resonance effect on amino acids adsorbed at the interfaces.

In this study we show a reproduction of the Zhadin experiment, which consists of the transient increase of the electrolytic current flow across an aqueous solution of L-arginine and L-glutamic acid induced by a proper low frequency alternating magnetic field superimposed to a static magnetic field of higher strength. We have identified the mechanisms that were at the origin of the so-far poor reproducibility of the above effect: the state of polarization of the electrode turned out to be a key parameter. The electrochemical investigation of the system shows that the observed phenomenon involves the transitory activation of the anode due to ion cyclotron frequency effect, followed again by anode passivation due to the adsorption of amino acid and its oxidation products. The likely occurrence of similar ion cyclotron resonance (ICR) phenomena at biological membranes, the implications on ion circulation in living matter, and the consequent biological impact of environmental magnetic fields are eventually discussed.

Adsorption↗
PubMed2005

Cefazolin concentrations in serum during cardiopulmonary bypass surgery.

The objective of the study was to investigate possible changes in cefazolin serum levels induced by cardiopulmonary bypass (CPB). Six cardiac male patients who underwent cardiac surgery requiring CPB took part in the study. Cefazolin 2 g was intravenously infused over 60 min before anesthesia and blood samples were taken at appropriate times after drug administration (0, 0.25, 0.5, 1, 4, 6, 8 h), 2 min before and 5 min after the beginning and 2 min before and 5 min after the end of CPB. Drug serum concentrations were determined by means of a microbiological method. Five minutes after the start of CPB, cefazolin serum levels decreased on average by 46.6% and remained steadily low until 5 min after the end of CPB. Then, they rose on average by 37.3% at 4 h and then declined slowly until the last sampling at 8 h. Cefazolin serum concentrations were low during CPB but remained in a potentially effective range for antimicrobial prophylaxis for this surgery.

Aged↗
PubMed2004

Prognostic factors in stage T1 grade 3 bladder cancer survival: the role of G1-S modulators (p53, p21Waf1, p27kip1, Cyclin D1, and Cyclin D3) and proliferation index (ki67-MIB1).

OBJECTIVE: To determine the prognostic value of a subset of regulators of the transition from G1-to-S phase of cell cycle in stage T1 grade 3 bladder cancers. METHODS: Fifty-one such cases were investigated to determine the significance on patient's survival of p53, p21Waf1, p27Kip1, Cyclin D1, Cyclin D3, and ki67-MIB1 (proliferation index). The statistical analysis included Kaplan-Meier methodology with Log-rank test and Cox' proportional hazard analysis. RESULTS: Tumor size (p=0.0034), and the labeling index of ki67-MIB1 (p=0.0034), p53 (p=0.0332), p27kip1 (p=0.0059) and Cyclin D1 (p=0.0103) were associated to disease-free survival. Progression-free survival was related to tumor size (p<0.0001), ki67 (p=0.0163), p53 (p=0.0041), p27kip1 (p=0.0161), Cyclin D1 (p<0.0001) and Cyclin D3 (p<0.0001). Patient's overall survival was associated to Cyclin D3 (p<0.0001), p53 (p=0.0017), p21Waf1 (p=0.0142), Cyclin D1 (p<0.0001), ki67-MIB1 (p=0.0450), and tumor size (p=0.0296). Down-regulation of p27kip1 and Cyclin D3 over-expression (disease-free), over-expression of p53, Cyclin D1 and Cyclin D3 (progression-free), and over-expression of Cyclin D3 (overall survival) were independent predictors by Cox's multivariate analysis. Down-regulation of p27kip1 (p<0.001, R.R. 0.997, 95%C.I. 0.995-0.999), and over-expression of Cyclin D1 (p<0.001, R.R. 1.009, 95%C.I. 1.004-1.014) and Cyclin D3 (p=0.005, R.R. 1.013, 95%C.I. 1.004-1.022) were the main independent predictors. CONCLUSION: Down-regulation of p27kip1 and over-expression of Cyclin D1 and Cyclin D3 might be relevant predictors of survival in stage T1 grade 3 bladder cancers, thus selecting a group of patients at higher risk of malignant behavior.

Adjuvants, Immunologic↗
PubMed2003

Immunocytochemical study by two photon fluorescence microscopy of the distribution of GABA(A) receptor subunits in rat cerebellar granule cells in culture.

An immunocytochemical investigation of the expression of alpha(1), alpha(6), beta(2/3), gamma(2) and delta subunits was performed on rat cerebellum granule cells in culture by the two photon microscopy technique. The first four subunits appear to be expressed abundantly in these cells, whereas the delta one seems to be expressed at a lower level. Another major difference in the distribution of these subunits is that whereas alpha(6), beta(2/3) and gamma(2) appear only on plasma membranes alpha(1) and delta are present mainly in the cell bodies cytoplasm. Still another difference was found in that the presence of gamma(2) on neurites is "polarized", preferentially labelling neurites with the appearance of dendrites. The subunits alpha(6) and beta(2/3) appear to label all types of neurites, with beta(2/3) being by far the most heavily expressed subunit type. A final distinct characteristic is that alpha(6) and, even more, gamma(2) appear to accumulate in the cytoplasmic domains immediately below the cone of emergence of neurites. This suggests a conspicuous transport of such subunits from the site of synthesis in the cell body to the site of final expression in the neurites (dendrites and axon terminals).

Animals↗
PubMed2002

Histological changes following two-step flap gastrocystoplasty in rats.

INTRODUCTION: A gastric segment used to increase bladder capacity can undergo considerable changes over time, as can all intestinal segments implanted in the urinary tract and in contact with urine. This experimental study reports the differences between the histological alterations observed in the gastric patch transposed in the bladder both with its own pedicle and after deafferentation from the stomach. MATERIALS AND METHODS: A group of 30 young male Sprague-Dawley rats underwent gastrocystoplasty. Survivors were divided into 3 groups: gastrocystoplasty alone (8 rats); gastrocystoplasty with vascular deafferentation at 15 days (7 rats), and at 2 months (8 rats). 5 rats were used as controls. Urinary pH was evaluated during a 6-month follow-up. RESULTS: Histology showed that early devascularization hindered the fusion of the two mucosae in the junctional area but reduced papillary hyperplasia (p = 0.013) of the gastric mucosa. No changes were observed in urinary pH after patch devascularization. CONCLUSIONS: Vascular deafferentation creates a gastric flap on the bladder which, even if it does not prevent urinary acidification, reduces the frequency of histologically detected changes susceptible for transformation into neoplasms.

Animals↗
PubMed2001

Occupational exposure to carbon black and risk of bladder cancer.

Exposure to carbon black has been linked to risk of lung and bladder cancer. We therefore investigated the frequency of these cancers in a group of 2286 longshoremen who were exposed occupationally to carbon-black dust. We identified 208 cancers (standardised incidence ratio 96, 95% CI 83-109), 53 lung cancers (108, 81-141), and 32 bladder cancers (130, 89-184). Longshoremen exposed to high concentrations of carbon black (n=14) had a significantly increased frequency of bladder cancer (204, 112-343). We conclude that the increase in bladder cancer in longshoremen is probably related to high exposure to carbon black.

Adult↗
PubMed2001

A historical cohort mortality study among shipyard workers in Genoa, Italy.

BACKGROUND: A historical cohort mortality study was conducted among 3984 shipyard workers assigned to ship repair, refitting, and construction in the harbor of Genoa, Italy, between 1960 and 1981. These workers were exposed to asbestos fibers, welding fumes and gases, silica dust, polycyclic aromatic hydrocarbons, and solvents. METHODS: Workers were classified in 20 different job-titles depending upon the type of activity. Standardized mortality ratios (SMRs) were computed using male residents of the Province of Genoa as the referent population. RESULTS AND CONCLUSIONS: For the whole cohort significantly increased SMRs were detected for all causes, all cancers, liver, larynx, lung, pleural and bladder cancers, respiratory tract diseases, and cirrhosis of the liver. The analysis by job-title showed increased SMRs not only for pleural cancer, but also for lung, laryngeal cancers and respiratory tract diseases in occupations entailing heavy asbestos exposure. Bladder and liver cancers and liver cirrhosis mortality also appeared to be related to occupational exposure.

Adult↗
PubMed2001

Secondary thyroid carcinoma after allogeneic bone marrow transplantation during childhood.

The aim of this study was to evaluate the incidence and risk factors related to secondary thyroid carcinoma (STC) in patients who have undergone allogeneic BMT during childhood. Data related to the primary hematological disorder and BMT procedure were obtained from the records of 113 patients (42 F; 71 M) who underwent BMT before the age of 18 (median 10.0 years; range 1.7-18.0) and survived more than 3 years after transplant with a median follow-up of 10.1 years (range 3.0-19.0). Sixteen received cranial radiation (CRT) during first-line treatment. Pre-transplant conditioning included TBI in 85 patients, TAI in two, while 26 children did not receive irradiation. The standardized incidence ratio of STC after BMT was significantly higher (P < 0.001) than that of the general population. STC was found in eight patients, 3.1 to 15.7 years after transplant. All received TBI and three also CRT. The Cox's regression analysis, although not statistically significant due to the small study population, showed an increased risk in those who had received a cumulative radiation dose higher than 10 Gy and in those who developed chronic GVHD. Careful follow-up of thyroid status including annual ultrasound examination is recommended for early detection of tumor.

Adolescent↗
PubMed2000

IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety.

The purpose of these guidelines is to provide concise guidance on the planning, performing and interpretation of studies to monitor groups or individuals exposed to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic agents have been shown to be carcinogenic in humans. Although the main interest in these studies is due to the association of genotoxicity with carcinogenicity, there is also an inherent interest in monitoring human genotoxicity independently of cancer as an endpoint. The most often studied genotoxicity endpoints have been selected for inclusion in this document and they are structural and numerical chromosomal aberrations assessed using cytogenetic methods (classical chromosomal aberration analysis (CA), fluorescence in situ hybridisation (FISH), micronuclei (MN)); DNA damage (adducts, strand breaks, crosslinking, alkali-labile sites) assessed using bio-chemical/electrophoretic assays or sister chromatid exchanges (SCE); protein adducts; and hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations. The document does not consider germ cells or gene mutation assays other than HPRT or markers of oxidative stress, which have been applied on a more limited scale.

Carcinogens↗
PubMed1999

Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: a study by the Working Party for Late Effects-EBMT.

Few data are available on the long-term effect of bone marrow transplantation (BMT) on growth. This study examines those factors that play a role in the final height outcome of patients who underwent BMT during childhood. Data on 181 of 230 patients with aplastic anemia, leukemias, and lymphomas who had BMT before puberty (mean age, 9.8 +/- 2.6 years) and who had reached their final height were analyzed. An overall decrease in final height standard deviation score (SDS) value was found compared with the height at BMT (P < 10(7)) and with the genetic height (P < 10(7)). Girls did better than boys, and the younger in age the person was at time of BMT, the greater the loss in height. Previous cranial irradiation + single-dose total body irradiation (TBI) caused the greatest negative effect on final height achievement (P < 10(4)). Fractionation of TBI reduces this effect significantly and conditioning with busulfan and cyclophosphamide seems to eliminate it. The type of transplantation, graft-versus-host disease, growth hormone, or steroid treatment did not influence final height. Irradiation, male gender and young age at BMT were found to be major factors for long-term height loss. Nevertheless, the majority of patients (140/181) have reached adult height within the normal range of the general population.

Adolescent↗
PubMed1999

Exposure to agrochemicals and DNA adducts in Western Liguria, Italy.

Pesticides are used to control pests and improve agricultural production. Despite their selectivity of action, a number of agrochemicals have been reported to be genotoxic using the (32)P-DNA postlabeling assay. Greenhouse floriculturists are suspected of being heavily exposed to agrochemicals during loading, mixing, and application of pesticides, as well as during manual activities by continuous contact with flowers and ornamental plants. We analyzed the DNA adduct formations in the white blood cells (WBCs) of 57 nonsmoker greenhouse floriculturists and 33 nonsmoker age-matched referents residing in the Western Liguria Region, Italy-the most important Italian greenhouse floriculture area. The averages of DNA adducts, expressed as relative adduct labeling (RAL), were 8.50 x 10(9) +/- 1.98 (SE) in floriculturists and 2.17 x 10(9) +/- 1.05 (SE) in referents. DNA adducts were significantly higher in floriculturists than in controls after adjustment for age and gender (P = 0.007). A specific adduct pattern, with up to six different spots, was observed in 60% of floriculturists, while no adducts were generally detected in controls. Our study represents an important contribution to the correct evaluation of the potential health risk associated with floriculture activity and supports the adoption of measures ensuring pesticide exposure reduction in greenhouses.

Adult↗
PubMed1999

Pre-clinical evaluation of new antineoplastic agents in NSCLC cell lines: evidence of histological subtype-dependent cytotoxicity.

The antiproliferative effect of paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cis-platin was studied on 5 non-small cell lung cancer (NSCLC) cell lines, 3 of which were adenocarcinoma (ADK) and 2 squamous cell carcinoma (SCC). Cellular chemosensitivity was determined using the MTT in vitro assay after 48, 72 and 96 h of exposure to drug in concentration ranging from 0.001 to 100 microM. A concentration-dependent cell growth inhibition was observed for paclitaxel, gemcitabine, topotecan, SN-38 and cis-platin in all cell lines tested. Docetaxel showed a concentration-independent cytotoxicity and was 104 times more potent than cis-platin (IC50 = 0. 001 vs. 10 microM). Paclitaxel, gemcitabine, topotecan and SN-38 were 102 times more potent than cis-platin, with median IC50 = 0.1 microM at 72 h. The level of drug-induced cell growth inhibition appeared to be correlated, for some of the six drugs tested, with the tumor histological subtype. In particular, topotecan and cis-platin were more active in squamous cell carcinoma than in adenocarcinoma cell lines (p=0.006 and 0.001 respectively at 0.1 microM concentration), while paclitaxel was more active in ADK than in SCC cell lines (p=0.004 at 0.01 microM concentration). Ca-Lu-6, a cell line that, contrary to most other lung cancer cell lines, is wild-type for most oncogenes/tumor suppressor genes, was by far the most sensitive cell line used (p=0.002, 0.003, 0.01 for paclitaxel, topotecan and cis-platin respectively, at 1 microM concentration), showing a >50% growth inhibition to new drugs at a concentration of 0.01 microM. In conclusion, all these new compounds tested were found to be more potent than cis-platin in affecting cellular proliferation of six NSCLC cell lines studied. We suggest that the specific histological subtype and molecular pattern of the cell line being treated could affect the antiproliferative effect of these drugs.

Adenocarcinoma↗
PubMed1998

Effects of cardio-pulmonary bypass on vancomycin plasma concentration decay.

The objective of the study was to investigate possible changes in vancomycin serum levels induced by cardio-pulmonary bypass (CPB). Ten cardiac patients (seven males, three females, aged between 56 and 81), who underwent cardiac surgery requiring CPB, took part in the study. Vancomycin (15 mg kg-1) was intravenously infused over 60 min before anaesthesia and blood samples were taken at appropriate times after drug administration (0, 0.5, 1, 6, 8 h), after starting CPB (0, 5, 30 and 60 min) and after aortic unclamping (0, 5, 30, 60, 120 min). Drug serum concentrations were determined by means of a fluorescence polarization immunoassay. The area under the concentration-time curve (AUC) measured during CPB were compared with the AUC extrapolated in the same interval by fitting a two-compartment pharmacokinetic model to drug concentrations obtained before and after CPB. Five minutes after starting CPB vancomycin serum levels decreased, on average, by 40.9% and remained steadily lower than the expected values over the next 60 min. In the same interval, the measured AUC was 31.7% lower than the expected AUC. In no instance did serum levels fall below the MIC for most common pathogens (1-2 mg l-1). At aortic unclamping serum levels slightly rebounded but tended to remain lower than the expected concentrations over the next 120 min. In conclusion, during CPB vancomycin serum levels invariably decreased but, at the dose employed (15 mg kg-1), remained in a potentially effective range for antimicrobial prophylaxis.

Aged↗
PubMed1998

Specific K-ras2 mutations in human sporadic colorectal adenomas are associated with DNA near-diploid aneuploidy and inhibition of proliferation.

Recent studies indicate that p21ras proteins mediate their multiple cell functions through interactions with multiple effectors and that the number of new effectors is growing. We recently reported that K-ras2 mutations in human colorectal adenomas were associated with chromosome instability and proliferation changes. In the present study, we extend these previous observations. Hereditary and multiple (n > or = 5) adenomas and adenomas with early cancer were excluded. Dysplasia was moderate in 91 cases and high in 25, and the median adenoma size was 1.5 cm. K-ras2 spectrum analysis was done by sequence-specific oligonucleotide hybridization using nuclear suspensions provided by analysis and sorting of multiparameter flow cytometry. In particular, tissue inflammatory cells were separated for DNA diploid tumors, whereas DNA aneuploid epithelial subclones were analyzed separately. K-ras2 mutations and DNA aneuploidy were both detected in 29 of 116 (25%) cases. DNA aneuploid index was in the near-diploid region in the majority of cases. DNA aneuploidy was strongly associated with G-->C/T transversions. An association was also found between low S-phase values and G-->A transitions. These findings were confirmed using multivariate logistic regression analysis to account for the effects of size, dysplasia, site, type, age, and sex. These data suggest that specific K-ras2 mutations in a subgroup of human sporadic colorectal adenomas play a role in chromosome instability and, contrary to expectations, are associated with inhibition of proliferation.

Adenoma↗
PubMed1998

32P-postlabeling detection of aromatic adducts in the white blood cell DNA of nonsmoking police officers.

Atmosphere in urban areas may be polluted by a number of combustion sources, including industries, vehicle traffic, and residential heating. Traffic police constitute a group of workers that is highly exposed to urban pollutants, especially those from motor vehicle exhaust. We conducted a biomonitoring study to simultaneously measure in 34 nonsmoking police officers and in 36 nonsmoking office workers, as referents, the individual benzo(a)pyrene [B(a)P] exposure using personal samplers and the formation of DNA adducts in peripheral WBCs using 32P-postlabeling techniques. Our results show that the police officers were exposed to significantly higher levels of B(a)P than were referents (P < 0.0001). No seasonal variation of the atmospheric levels of B(a)P was found throughout the year. The median relative adduct labeling x 10(-8) values of the controls and exposed police officers were 0.94 (range, 0.1-3.7) and 1.3 (range, 0.1-5.5), respectively, using the nuclease P1 technique. Although the DNA adduct levels of police officers were globally higher than those of referents (P < 0.05), the difference was entirely due to the summer difference [median values 0.80 (range, 0.1-1.8) and 2.8 (range, 0.7-5.5), respectively (P < 0.001)]. In winter, the DNA adduct levels were substantially identical, and in midseason, there was only a very small increase in police officers, with respect to controls (statistically not significant). Moreover, a more significant seasonal variation of bulky aromatic DNA adduct levels was observed in WBC DNA samples of police officers (P < 0.05) compared to those of referents. The seasonal variation of bulky aromatic adduct levels could be correlated with the reported seasonal variation of aryl hydrocarbon hydroxylase inducibility in human lymphocytes.

Adult↗
PubMed1998

Urinary excretion of 1-hydroxypyrene as a marker for exposure to urban air levels of polycyclic aromatic hydrocarbons.

A cross-sectional study was conducted among 94 traffic police officers from the Municipality Police of Genoa, Italy, exposed to airborne pollutants and 52 referent subjects exposed to indoor air pollution levels to investigate the relationships between exposure to ambient air polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene (1-OH-P). The effects of smoking, lifestyle factors such as exposure to ETS, and diet, along with the role played by the cytochrome P4501A1 (CYP1A1), and glutathione S-transferase M1 and theta metabolic susceptibility gene polymorphisms were examined. The geometric mean of benzo(a)pyrene air measurements (an index compound of PAH levels) was 70 times higher in traffic police officers (3.67 ng/m3) than in referents (0.05 ng/m3). The urinary concentration of 1-OH-P was clearly associated with cigarette smoking and, to a lesser extent, with exposure to ETS and particulate PAH pollution. No association was detected between 1-OH-P excretion and diet. Women exhibited a higher excretion level than did men, and an apparent effect of age was due to differences in cigarette smoking habits. Exposure to PAHs resulted in higher levels of 1-OH-P excretion in all groups except heavy smokers. Overall, no significant role of any metabolic polymorphism was detected. However, stratification of study subjects according to their smoking habits revealed higher levels of excretion of 1-OH-P in subjects smoking < or =15 cigarettes/day carrying the CYP1A1 polymorphism. No such effect was seen either with nonsmokers or with people smoking more than 15 cigarettes/day. These findings are suggestive of a gene-environment interaction, in which subjects with the CYP1A1 polymorphism, relative to subjects without it, have higher levels of 1-OH-P in their urine at low doses of exposure to PAHs.

Age Distribution↗
PubMed1997

Sister chromatid exchange induction in peripheral blood lymphocytes of traffic police workers.

Traffic police workers, as a population exposed to urban atmosphere, were compared with a control population exposed to indoor air pollution levels. Sister chromatid exchanges (SCEs) as a biomarker of effect were measured in peripheral blood lymphocytes of 54 exposed subjects and 35 controls, and environmental concentration of polynuclear aromatic hydrocarbon (PAH) tracer compounds was detected by personal air samplers. The mean exposure level to benzo[a]pyrene in our group of traffic policemen (3.4 mg/m3) was in the range that has been estimated in urban areas in Europe during the last 10 years. No difference in SCE levels was found between exposed workers (7.36, SD 1.35) and controls (7.47, SD 1.28). No correlation was observed between SCE/cell and airborne PAH concentration in the traffic worker population. A positive regression of SCE on exposure estimate was found only in the non-smoking group of police workers. Our findings suggest that exposure to urban air pollution does not induce relevant cytogenetic effects.

Adult↗