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ABSTRACT: BACKGROUND: Single wall carbon nanotubes (SWCNTs) are considered promising nanoparticles for industrial and biomedical applications; however their potential toxicity in several biological systems, including the feto-placental unit, has been demonstrated. Functionalization of SWCNTs with polyethylene glycol chains (PEG-SWCNTs) dramatically reduces their toxicity, and for this reason PEG-SWCNTs are candidates for biomedical applications. However, no data are available on their safety for the developing embryo, in spite of the clinical and social relevance of this topic. The purpose of this study is therefore to investigate the safety of PEG-SWCNTs for their use as biomedical carriers in pregnancy. METHODS: For toxicological studies, amino-functionalized PEG-SWCNT were intravenously injected in CD1 pregnant mice at different doses (range 0.1-30 mug/mouse), in single or multiple administrations. For biodistribution studies, fluorescently labeled PEG-SWCNTs were obtained by acylation of terminal PEG amino groups with near infrared emitting fluorochromes (PEG-SWCNT-750) and injected at the dosage of 10 mug/mouse, at either day 5.5 (when the placenta is still developing) or day 14.5 of gestation (when the maturation of the placenta is complete). RESULTS: We found no adverse effects both on embryos and dams up to the dose of 10 mug/mouse. At the dose of 30 mug/mouse, occasional teratogenic effects, associated with placental damage, were detected both when administered as a single bolus (1 out of 10 dams; 1 malformed embryo) or as multiple doses (2 out of 10 dams; 5 malformed embryos). The difference in the prevalence of dams with malformed embryos between the 30 mug exposed group and controls approached the statistical significance (p = 0.06). Hepatic damage in dams was seen only in the multiple exposure group (4 out of 10; p = 0.04 when compared with the single exposure group or controls). PEG-SWCNT-750 reached the conceptus when administered early in pregnancy. At later stages, PEG-SWCNT-750 were detected in the placenta and the yolk sac, but not in the embryo. CONCLUSIONS: PEG-SWCNTs may cause occasional teratogenic effects in mice beyond a threshold dose. Such effect might depend on their ability to reach the feto-placenta unit. Although not automatically transferable to humans, these data should be considered if exposing women during pregnancy.
Particle and Fibre Toxicology 06/2013; 10(1):21. · 7.25 Impact Factor
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ABSTRACT: Due to the increasing use of engineered nanoparticles in many consumer products, rapid and economic tests for evaluating possible adverse effects on human health are urgently needed. In the present chapter the use of mouse embryonic stem cells as a valuable tool to in vitro screen nanoparticle toxicity on embryonic tissues is described. This in vitro method is a modification of the embryonic stem cell test, which has been widely used to screen soluble chemical compounds for their embryotoxic potential. The test offers an alternative to animal experimentation, reducing experimental costs and ethical issues.
Methods in molecular biology (Clifton, N.J.) 04/2013;
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Antonio Pietroiusti,
Micol Massimiani,
Ivana Fenoglio,
Massimiliano Colonna,
Federica Valentini,
Giuseppe Palleschi,
Antonella Camaioni,
Andrea Magrini,
Gregorio Siracusa,
Antonio Bergamaschi,
Alessandro Sgambato,
Luisa Campagnolo
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ABSTRACT: Several in vitro and in vivo studies suggest local and systemic effects following exposure to carbon nanotubes. No data are available, however, on their possible embryotoxicity in mammals. In this study, we tested the effect of pristine and oxidized single-wall carbon nanotubes (SWCNTs) on the development of the mouse embryo. To this end, SWCNTs (from 10 ng to 30 μg/mouse) were administered to female mice soon after implantation (postcoital day 5.5); 10 days later, animals were sacrificed, and uteri, placentas, and fetuses examined. A high percentage of early miscarriages and fetal malformations was observed in females exposed to oxidized SWCNTs, while lower percentages were found in animals exposed to the pristine material. The lowest effective dose was 100 ng/mouse. Extensive vascular lesions and increased production of reactive oxygen species (ROS) were detected in placentas of malformed but not of normally developed fetuses. Increased ROS levels were likewise detected in malformed fetuses. No increased ROS production or evident morphological alterations were observed in maternal tissues. No fetal and placental abnormalities were ever observed in control animals. In parallel, SWCNT embryotoxicity was evaluated using the embryonic stem cell test (EST), a validated in vitro assay developed for predicting embryotoxicity of soluble chemical compounds, but never applied in full to nanoparticles. The EST predicted the in vivo data, identifying oxidized SWCNTs as the more toxic compound.
ACS Nano 06/2011; 5(6):4624-33. · 10.77 Impact Factor
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ABSTRACT: Previous separate studies have shown associations of coronary artery disease (CAD) with acid phosphatase locus 1 (ACP1) and adenosine deaminase locus 1 (ADA1) genetic polymorphisms. Because it is known that the 2 systems interact and have important immunologic and metabolic functions, these 2 genes were both examined in the same sets of subjects.
Two-hundred forty subjects with CAD, 156 subjects with cardiovascular diseases without CAD, 279 subjects with Non Insulin Dependent Diabetes Mellitus (NIDDM) without CAD and 771 consecutive healthy newborn infants have been studied.
The association of ACP1 and ADA1 with CAD depends on sex and diabetes. In particular, the association between ADA1 and CAD is present in nondiabetic subjects only, and it is dependent on sex (males), whereas the association of CAD with ACP1 is present in diabetic subjects only, and it is dependent on sex (females).
The fact that the association of ACP1 with CAD is evident only in diabetic subjects, whereas the association of ADA1 with CAD is evident only in nondiabetic subjects suggests an heterogeneity in the pathogenetic mechanisms leading to CAD. In addition, the association with sex that could be based on hormonal differences is in favor of heterogenity.
The American Journal of the Medical Sciences 08/2010; 340(2):103-8. · 1.39 Impact Factor
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ABSTRACT: Cement is widely used for construction and several reports have suggested a potential toxicity of cement dusts although it has never been definitively assessed. To determine the cytotoxic and bioactive effects of cement dusts, cultures of normal rat fibroblasts were exposed to different types of cements and cell growth parameters, apoptosis and the occurrence of DNA damage (both in terms of DNA breaks and oxidative damage) were analyzed. Cells were exposed to cement extracts or cultured in direct contact with cement dusts and the results obtained were compared to cells cultured in fresh medium. A dose-dependent decrease in viable cells was observed with all tested cements. Different results were obtained in the cell-cement direct contact tests compared to the indirect contact tests performed using extracts. Inhibition of cell growth was associated in most cases with an accumulation of cells in the S-phase of the cell-cycle and the appearance of an apoptotic peak. DNA strand breaks, assessed by comet test, and increase in the levels of 8-OHdG, an important marker of DNA oxidative damage, always occurred by incubating cells in the presence of cement extracts or dusts. However, after removal of cement, a rapid damage repair was generally observed with an almost complete recovery within 12 hours. In conclusion, all cements analyzed in this study displayed a limited toxicity in vitro without significant differences amongst them. Overall, the results obtained indicate that cements should be treated as hazardous materials but they do not allow to make accurate predictions regarding the in vivo effects. Further studies are warranted to reach a better understanding of the potential toxic effects of cements, to identify the responsible mechanisms and to evaluate the possibility of modulating and/ or preventing them.
Toxicology and Industrial Health 04/2010; 26(5):309-17. · 1.42 Impact Factor
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ABSTRACT: Night-shift work is associated with ischaemic cardiovascular disorders. It is not currently known whether it may be causally linked to metabolic syndrome (MS), a risk condition for ischaemic cardiovascular disorders. The syndrome presents with visceral obesity associated with mild alterations in glucidic and lipidic homeostasis, and in blood pressure. The aim of this study was to assess whether a causal relationship exists between night-shift work and the development of MS.
Male and female nurses performing night shifts, free from any component of MS at baseline, were evaluated annually for the development of the disorder during a 4-year follow-up. Male and female nurses performing daytime work only, visited during the same time period, represented the control group.
The cumulative incidence of MS was 9.0% (36/402) among night-shift workers, and 1.8% (6/336) among daytime workers (relative risk (RR) 5.0, 95% CI -2.1 to 14.6). The annual rate of incidence of MS was 2.9% in night-shift workers and 0.5% in daytime workers. Kaplan-Meier survival curves of the two groups were significantly different (log-rank test; p<0.001). Multiple Cox regression analysis (forward selection method based on likelihood ratio) showed that among selected variables (age, gender, smoking, alcohol intake, familiar history, physical activity, and work schedule) the only predictors of occurrence of MS were sedentariness (hazard ratio (HR) 2.92; 95% CI 1.64 to 5.18; p = 0.017), and night-shift work (HR 5.10; 95% CI 2.15 to 12.11; p<0.001).
The risk of developing MS is strongly associated with night-shift work in nurses. Medical counselling should be promptly instituted in night-shift workers with the syndrome, and in case of persistence or progression, a change in work schedule should be considered.
Occupational and environmental medicine 09/2009; 67(1):54-7. · 3.64 Impact Factor
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Occupational Medicine 01/2009; 58(8):587-90. · 1.14 Impact Factor
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ABSTRACT: CagA-positive Helicobacter pylori infection has been found to be associated with a first-ever atherosclerotic stroke. The aim of this study was to investigate whether these strains represent an independent risk factor for recurrent atherosclerotic stroke.
We performed a longitudinal study of patients with a first-ever large vessels stroke and resulted positive at H. pylori serology. Patients had clinical examination 1 month after the acute event, and were subsequently visited or contacted by telephone up to 3 years at 6-month intervals. Sera obtained at the time of enrollment were frozen and analyzed for the presence of anti-CagA antibodies at the end of the study. The primary outcome event was any fatal or nonfatal stroke after the index stroke.
One hundred seventy H. pylori-positive patients were included (n = 68 CagA positive and n = 102 CagA negative). No significant difference regarding age and other stroke risk factors was detected. According to Kaplan-Meier survival analysis, CagA-positive patients showed a significantly higher risk for stroke recurrence than CagA-negative ones (45.6% vs 17.6%; p < .001). Difference in the rate of recurrent stroke between the two groups persisted after Cox regression analysis taking into account possible confounding factors (hazard ratio = 3.5; 95% CI = 1.9-6.4; p < .001).
Infection with H. pylori CagA-positive strains increases the risk of recurrent atherosclerotic stroke. Seropositivity determination should be performed in order to identify high-risk patients requiring a strict clinical surveillance, and the possible beneficial effect of eradication therapy should be evaluated.
Helicobacter 12/2008; 13(6):525-31. · 3.15 Impact Factor
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ABSTRACT: No data are currently available on the prevalence and characteristics of functional dyspepsia among cement workers. Given the potential impact of dyspepsia on work performance, whether its prevalence is increased among workers exposed to cement dust was evaluated.
Altogether 420 cement workers were enrolled in the study. According to the individual exposure levels to cement dust, the following three groups were established: no exposure (128 workers), low exposure (1 mg/m3, 176 workers). Dyspepsia was evaluated by means of validated questionnaires.
The prevalence of dyspepsia was increased in both the low and high exposure groups in comparison with the unexposed workers (51.7% and 59.1%, respectively, versus 34.4%; adjusted odds ratio (aOR) 2.21, 95% confidence interval (95% CI) 1.25-3.92, and aOR 2.36, 95% CI 1.31-4.25, respectively). A stepwise regression analysis showed a progressive increase in the odds ratio for dyspepsia for the low- and high-exposure groups with the no-exposure group as reference (OR 1.94, 95% CI 1.15-3.27, and OR 2.61, 95% CI 1.62-4.20, respectively). Ulcer-like dyspepsia was especially associated with the degree of exposure to cement dust, 11.71% for the no-exposure group versus 17.24% for the low-exposure group versus 29.54% for the high-exposure group (aOR 3.49, 95% CI 1.60-7.63), when the high-exposure group was compared with the no-exposure group. Similar findings were obtained for reflux-like dyspepsia.
Occupational cement-dust exposure is associated with dyspepsia, and the association is particularly strong for ulcer-like and reflux-like dyspepsia.
Scandinavian journal of work, environment & health 11/2008; 34(5):396-402. · 3.12 Impact Factor
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ABSTRACT: It has been suggested that extended high-frequency audiometry (EHFA) might be more sensitive than conventional audiometry in detecting early signs of hearing impairment. However, this technique has not been adequately tested in an occupational environment. We therefore investigated the usefulness of this method in noise-exposed workers.
We compared conventional frequency audiometry (0.25-8 kHz) and EHFA (9-18 kHz) in 184 noise-exposed and 98 non-noise-exposed workers.
Both methods showed significantly higher threshold levels (P < 0.05) in noise-exposed workers for most of the tested frequencies; however, the differences were more marked for EHFA, especially in young exposed workers. Significant differences in the EHF range were detected also in the subgroup of noise-exposed workers with normal findings at conventional audiometry. Stepwise regression analysis showed that in 21- to 40-year-old workers the noise effect was largely predominant at both conventional audiometry and EHFA, whereas in older subjects the noise effect was predominant up to 6 kHz frequency, the effect of age being significantly greater at higher frequencies.
These data indicate that EHFA is more sensitive than conventional audiometry in detecting noise induced hearing loss. However, hearing loss in the EHF range seems an age-dependent phenomenon with progression into the lower speech range frequencies with increasing age. These changes seem to be accentuated in the early years by noise exposure, suggesting that EHFA could represent a useful preventive measure in young exposed workers.
American Journal of Industrial Medicine 06/2008; 51(6):452-62. · 1.63 Impact Factor
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ABSTRACT: To evaluate whether some duodenal ulcers (DU) classified as idiopathic according to standard criteria may be causally related to isolated duodenal colonization by H. pylori.
We studied consecutive ambulatory patients undergoing upper gastrointestinal endoscopy in a secondary care setting. Gastric and duodenal biopsies for diagnosing H. pylori infection were taken from all patients. Independently from the findings of duodenal biopsies, DU patients without gastric infection were classified as having idiopathic ulcers, and underwent urea C13 breath test and subsequent eradication therapy. Endoscopy was repeated 6 months after eradication treatment.
Among 608 DU patients, 42 (6.9%) were classified as idiopathic: 24 (3.9%) were free from gastric and duodenal infection (group A) and 18 (3.0%) (group B) had isolated duodenal colonization. Urea C13 breath test was positive in one (4.2%) group A patient and in 3 (16.7%) group B patients. After eradication therapy, DU were detected in 14 out of 20 group A patients (70%) (four patients did not perform control endoscopy) and in 2 group B patients (11.1%): OR 18.66, 95% CI 3.23-107.82, P= 0.002. The difference was still detectable after multivariate analysis taking into account possible confounding factors: OR 15.79, 95% CI 2.48-100.53, P= 0.001.
Isolated duodenal colonization by H. pylori is detectable in a substantial proportion of patients with so-called idiopathic DU, and eradication therapy is effective in these patients.
The American Journal of Gastroenterology 02/2008; 103(1):55-61. · 7.28 Impact Factor
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ABSTRACT: The approach to the treatment of Helicobacter pylori infection has changed during the last years. In fact, during the last decade, the success rate of usual eradication regimens, based on a proton pump inhibitor plus clarithromycin associated with amoxicillin or metronidazole, declined from over 90% to about 80%, a critical threshold under which the eradication rate is considered unsatisfactory, according to current guidelines. This finding is mainly due to the raising prevalence of clarithromycin resistance, which is in turn linked to the widespread use of this antibiotic for respiratory tract infections. Therefore, obtaining a personal history negative for a previous use of macrolides is now mandatory, before administering clarithromycin-based antibiotic therapy. Should history data be uncertain, local resistance rates (if available) may be considered, with levels higher than 20% precluding the use of clarithromycin. In this case, alternative antibiotic combinations, previously used in the rare instances of failure of clarithromycin-based therapy, should be used. We examined also the possible additional beneficial effect of some novel non antibiotic agents such as lactoferrin, probiotics and natural substances. Other advances in the treatment of the infection are represented by the discovery that some extragastric disorders such as unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, may be causally linked to Helicobacter pylori, and that eradication therapy may lead to their regression in many cases. Finally, some "gray areas" (nonulcer dyspepsia, concomitant use of nonsteroidal anti-inflammatory drugs) which are the subject of debate as far the indication to treatment is concerned, have been discussed.
Recent Patents on Anti-Infective Drug Discovery 12/2007; 2(3):197-205.
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Journal of Epidemiology 10/2006; 16(5):220; author reply 221. · 1.86 Impact Factor
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Stroke 07/2006; 37(6):1361; author reply 1362. · 5.73 Impact Factor
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Diabetes Care 07/2006; 29(6):1399-401. · 8.09 Impact Factor
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ABSTRACT: The involvement of Helicobacter pylori in the pathogenesis of extragastric diseases continues to be an interesting topic in the field of Helicobacter-related pathology. Although conflicting findings have been reported for most of the disorders, a role of H. pylori seems to be important especially for the development of cardiovascular and hematologic disorders. Previously isolated human and animal Helicobacter sp. flexispira and "Helicobacter heilmannii" strains have been validated using polyphasic taxonomy. A novel enterohepatic Helicobacter has been isolated from mastomys and mice, adding to the list of helicobacters that colonize the liver. Genetic targets that may aid the classification of novel Helicobacter species have emerged. Animal models of Helicobacter-induced gastric and hepatobiliary diseases have offered insights to the mechanisms associated with premalignant transformation.
Helicobacter 02/2005; 10 Suppl 1:54-65. · 3.15 Impact Factor
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ABSTRACT: The recognition of the role of Helicobacter pylori in gastric diseases has led to the widespread use of antibiotics in the eradication of this pathogen. The most advocated therapy, triple therapy, often includes clarithromycin. It is well known that clarithromycin resistance is one of the major causes of eradication failure. The development of a rapid noninvasive technique that could easily be performed on fecal samples and that could also provide information about the antibiotic resistance of this microorganism is therefore advisable. Previous findings have demonstrated that clarithromycin resistance is due to a single point mutation in the 23S rRNA. All the mutations described have been associated with specific restriction sites, namely BsaI (A2143G), MboII (A2142C/G), and HhaI (T2717C). On this basis we have developed a new method, a seminested PCR, allowing screening for clarithromycin resistance of H. pylori directly on stool samples. This method furnished a 783-bp fragment of the 23S rRNA, which was subsequently digested by MboII, BsaI, and HhaI, in order to identify single point mutations associated with clarithromycin resistance. Of a total of 283 stool samples examined, 125 were H. pylori positive and two of them were shown to contain clarithromycin-resistant strains due to the presence of a mutation at position 2717, whereas no PCR products contained mutations at position 2142 or 2143. In order to evaluate the reliability of the new system, we compared the results of restriction analysis of the PCR products with the MICs shown by the H. pylori isolates by culturing gastric biopsies from the same patients.
Journal of Clinical Microbiology 09/2003; 41(8):3636-40. · 4.15 Impact Factor
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ABSTRACT: Resistance of Helicobacter pylori to clarithromycin occurs with a prevalence ranging from 0 to 15%. This has an important clinical impact on dual and triple therapies, in which clarithromycin seems to be the better choice to achieve H. pylori eradication. In order to evaluate the possibility of new mechanisms of clarithromycin resistance, a PCR assay that amplified a portion of 23S rRNA from H. pylori isolates was used. Gastric tissue biopsy specimens from 230 consecutive patients were cultured for H. pylori isolation. Eighty-six gastric biopsy specimens yielded H. pylori-positive results, and among these 12 isolates were clarithromycin resistant. The latter were studied to detect mutations in the 23S rRNA gene. Sequence analysis of the 1,143-bp PCR product (portion of the 23S rRNA gene) did not reveal mutation such as that described at position 2142 to 2143. On the contrary, our findings show, for seven isolates, a T-to-C transition at position 2717. This mutation conferred a low level of resistance, equivalent to the MIC for the isolates, selected using the E-test as well as using the agar dilution method: 1 micro g/ml. Moreover, T2717C transition is located in a highly conserved region of the 23S RNA associated with functional sites: domain VI. This fact has a strong effect on the secondary structure of the 23S RNA and on its interaction with macrolide. Mutation at position 2717 also generated an HhaI restriction site; therefore, restriction analysis of the PCR product also permits a rapid detection of resistant isolates.
Antimicrobial Agents and Chemotherapy 01/2003; 46(12):3765-9. · 4.84 Impact Factor
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Antonio Pietroiusti,
Marina Diomedi,
Mauro Silvestrini,
Letizia Maria Cupini,
Ida Luzzi,
Maria Jesus Gomez-Miguel,
Antonio Bergamaschi,
Andrea Magrini,
Tiziana Carrabs,
Marina Vellini,
Alberto Galante
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ABSTRACT: It is uncertain whether Helicobacter pylori is associated with ischemic syndromes and whether this association is mediated by the induction of atherosclerosis. In this study, we tested the hypothesis that atherosclerotic stroke shows a selective association with virulent H pylori strains.
The seroprevalence of infection by H pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, was assessed by ELISA in 138 patients with large-vessel stroke (group A), in 61 patients with cardioembolic stroke (group B), and in 151 healthy control subjects. The 3 groups had a similar socioeconomic status. Serum levels of C-reactive protein were also measured by ELISA. The prevalence of infection was 71% in group A, 63.9% in group B, and 70.2% in the control group (P=NS), whereas the prevalence of CagA-positive strains was higher in group A than in group B (42.8% versus 19.7%, respectively; odds ratio 3.04, 95% CI 1.43 to 6.49; P<0.001) and higher in group A than in the control group (42.8% versus 17.9%, respectively; odds ratio 4.3, 95% CI 2.12 to 8.64; P<0.001), after adjusting for main cardiovascular risk factors and social class. A trend toward a difference in C-reactive protein was observed between CagA-positive (2.00+/-3.43 [mean+/-SD] mg/dL) and CagA-negative (1.31+/-1.72 [mean+/-SD] mg/dL) patients (P=0.072, Mann-Whitney U test).
The association between H pylori and acute cerebrovascular disease seems to be due to a higher prevalence of more virulent H pylori strains in patients with atherosclerotic stroke.
Circulation 07/2002; 106(5):580-4. · 14.74 Impact Factor
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ABSTRACT: To determine how often primary care physicians prescribe eradication therapy for peptic ulcer disease (PUD) and nonulcer dyspepsia (NUD).
During a 2-year period (1998-2000) we analyzed data concerning patients with PUD or NUD seen by 80 Italian primary care physicians uniformly distributed throughout the country. We classified patients as having a definitive or a presumptive diagnosis on the basis of the completeness of the diagnostic workup and interpreted the prescription of antibiotics for dyspepsia as evidence of attempted eradication of Helicobacter pylori.
Consecutive ambulatory patients.
The frequency with which predefined groups of patients received eradication therapy.
Of 6866 patients, 690 (10%) received eradication therapy. Of 2162 patients with PUD, 596 (27.6%) received eradication therapy; of 4704 patients with NUD, however, only 94 (2%) received this treatment (P =.0001). A total of 341 (37.7%) of 904 PUD patients with a definitive diagnosis were given eradication therapy and 255 (20.3%) of 1258 PUD patients with a presumptive diagnosis were given therapy (P <.0001). In NUD patients, 7 of 743 (0.9%) with a definitive diagnosis received eradication therapy, while 87 (2.2%) of 3961 of those with a presumptive diagnosis were given the same therapy (P =.025).
While Italian primary care physicians appropriately target eradication therapy for H pylori infection in patients with peptic ulcer disease rather than nonulcer disease, the intervention was still underused in these patients. Improvements in this prescribing behavior are needed.
The Journal of family practice 03/2002; 51(3):265. · 0.61 Impact Factor
