1,721,214 research outputs found
Exposure to pesticides and risk of amyotrophic lateral sclerosis: a population-based case-control study
No full textBackgroud: A few epidemiologic studies suggested an association of agricultural work and pesticides exposure with a severe degenerative disease of the motor neurons, amyotrophic lateral sclerosis (ALS), though conflicting results have also been provided. Some laboratory investigations have also provided biological plausibility for this hypothesis, indicating that pesticides might adversely affect the motor neurons.Objective: We investigated through a population-based case-control study the possible relation between pesticides and ALS in the northern Italy municipality of Reggio Emilia. Methods: By administering a questionnaire, we investigated occupational history and leisure time habits of the 41 ALS patients diagnosed in the 1995-2006 period, and of 82 age- and sex-matched randomly sampled population controls, to ascertain the regular use of pesticides. All cases of ALS appeared to be of the sporadic form of the disease and were classified as ‘certain’ or ‘probable’ forms of the disease, according to the so-called ‘El Escorial criteria’.Results: More cases than controls were found to have been exposed to pesticides for at least six months (31.7% versus 13.4%, respectively), in all cases within the occupational environment. In a conditional logistic regression model, we found an excess ALS risk associated with exposure to pesticides, with an odds ratio of 3.6 and a 95% confidence interval of 1.2-10.5. Inclusion in the statistical analysis of potential confounders, such as electromagnetic fields exposure and drinking water chemical composition, did not modify such association and it even enhanced it
Editorial: Pathoblockers and antivirulence agents of plant-origin for the management of multidrug resistant pathogens
No full textMission & scope. Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Paul D. Cotter at Teagasc Food Research Centre is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide
Data from molecular mechanism investigation on new purposely designed hybrid compounds to inhibit NDH-2 enzyme of P. falciparum and S. aureus
No full textA series of hybrid compounds has been designed and synthesized by linking the pharmacophore of the antimalarial drug chloroquine with the phenothiazine core. The dataset contains the free induction decay (fid) of 1H and 13C NMR spectra registered on a Bruker spectrometer working at 600 MHz and at 150 MHz of the new compounds and the optical density measurements of the microbial and cellular growths of the experimental model systems treated with the hybrid compounds
Enhanced inhibition of parvovirus B19 replication by cidofovir in extendedly exposed erythroid progenitor cells
No full textHuman parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying haematological disorders or with immune system deficits. Currently, therapeutic options for B19V entirely rely on symptomatic and supportive treatments since a specific antiviral therapy is not yet available. Recently a first step in the research for active compounds inhibiting B19V replication has allowed identifying the acyclic nucleoside phosphonate cidofovir (CDV). Herein, the effect of CDV against B19V replication was characterized in human erythroid progenitor cells (EPCs) cultured and infected following different experimental approaches to replicate in vitro the infection of an expanding erythroid cell population in the bone marrow. B19V replication was selectively inhibited both in infected EPCs extendedly exposed to CDV 500 μM (viral inhibition 82%) and in serially infected EPCs cultures with passage of the virus progeny, constantly under drug exposure (viral inhibition 99%). In addition, a potent inhibitory effect against B19V (viral inhibition 92%) was assessed in a short-term infection of EPCs treated with CDV 500 μM 1 day before viral infection. In the evaluated experimental conditions, the enhanced effect of CDV against B19V might be ascribed both to the increased intracellular drug concentration achieved by extended exposure, and to a progressive reduction in efficiency of the replicative process within treated EPCs population
Inhibitory effect of Cidofovir on Parvovirus B19 replication
No full textParvovirus B19 (B19V) is a human ssDNA virus responsible for a wide range of clinical manifestations, still lacking for a specific
antiviral therapy. The identification of compounds active against B19V may add therapeutic options to the treatment of B19V
infections. To this purpose, focus was raised to cidofovir (CDV), an acyclic nucleoside phosphonate broadly active against dsDNA
viruses.
Two model systems were used to assess the inhibitory effect of CDV on B19V replication: 1) the UT7/EpoS1 megakaryoblastoid cell
line, able to support B19V DNA replication; 2) the ex vivo expanded CD36+ erythroid progenitor cells (EPCs), a highly permissive
system for B19V replication and expression. EPCs were generated from peripheral blood, via culture in a medium containing
erythropoietic growth factors (EPO, SCF and Il-3), for up to 18 days. Expression of EPC differentiation markers ranged from a
minimum of 10% at 3-day to a 80% at 15-day culturing. Infection at different stages indicated that the EPC system was fully
permissive to B19V between days 6 and 15 of EPCs in vitro growth and differentiation.
Experiments were carried out at different multiplicity of infection (100 – 104 genomes/cell) and CDV concentrations (0.1 – 500 μM).
The effects of CDV were evaluated by its capacity to inhibit viral nucleic acid synthesis, as determined by means of q PCR assays
for quantification of viral nucleic acids. CDV showed a dose-dependent inhibiting activity on B19V replication within infected UT7/
EpoS1, allowing for the determination of EC50 and EC90 values (7.45–41.27 μM, and 84.73–360.7 μM, respectively). In EPCs, a
significant reduction on B19V DNA amounts was obtained only at 500 μM (68.2–92.8%). However, cell-culture supernatants from
B19V-infected, CDV-treated EPCs were used for serial infection of EPCs in the presence of CDV, leading to a progressive inhibition
of B19V replication compared to untreated controls.
With regard to the host cells, the drug did not interfere with the overall cellular DNA replication and metabolic activity. The effect of
CDV on B19V could be likely related to a specific inhibition on the viral replication process, indicating the possibility of developing
an antiviral strategy against a relevant human pathogenic virus
The epidemiology of amyotrophic lateral sclerosis in Reggio Emilia, Italy
No full textIncidence and mortality rates of amyotrophic lateral sclerosis (ALS) vary between countries, and in some studies appear to increase over time. We performed a study to assess ALS incidence in a northern Italy area over a 10-year period. We identified the new cases of probable or definite ALS diagnosed among residents in Reggio Emilia province between 1996 and 2005 using several sources of data, such as death certificates, clinical records, hospital discharge registers and drug prescriptions. A total of 94 newly-diagnosed patients were identified. The average standardized incidence in the period was 2.0 and 1.0 cases/100,000/year, using the Italian and the world population, respectively, as reference. There was no variation in rates over time. Incidence was 1.3 in males and 0.8 in females. No cases were observed in patients under 35 years of age. Incidence increased after the age of 55 years, reaching a peak in the group aged 70-74 years and declining thereafter. We concluded that ALS incidence in this population was similar to that observed in other Italian regions and European countries, and no variation was identified during the study period
Inhibition of Parvovirus B19 replication by Cidofovir in extendedly exposed erythroid progenitor cells
No full textHuman parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying hematological disorders or with immune system deficits. Currently, therapeutic options for B19V entirely rely on symptomatic and supportive treatments since a specific antiviral therapy is not yet available. Recently a first step in the research for active compounds inhibiting B19V replication has allowed identifying the acyclic nucleoside phosphonate cidofovir (CDV). Herein, the effect of CDV against B19V replication was characterized in human erythroid progenitor cells (EPCs) cultured and infected following different experimental approaches to replicate in vitro the infection of an expanding erythroid cell population in the bone marrow. B19V replication was selectively inhibited both in infected EPCs extendedly exposed to CDV 500 μM (viral inhibition 82%) and in serially infected EPCs cultures with passages of the viral progeny, constantly under drug pressure (viral inhibition >99%). In addition, a potent inhibitory effect against B19V (>92%) was assessed in a short-term infection of EPCs treated with CDV 500 μM prior to viral infection. This enhanced anti-B19V activity of CDV could be ascribed both to the increased intracellular drug concentration achieved by extended exposure, and to a progressive reduction in efficiency of the replicative process within treated EPCs population
Possible involvement of environmental selenium in the etiology of amyotrophic lateral sclerosis
No full textThe metalloid selenium (Se) is of considerable interest in environmental health, since it has both toxicological and nutritional properties, though these potential effects are still debated and not entirely elucidated. The safe range of Se intake in the human has not been clearly defined, but it appears to be very narrow, as also confirmed by recent epidemiologic and laboratory studies. Moreover, it is well recognized that the different Se compounds have distinctive biological activities, and the inorganic species appear to be the most toxic ones, despite being retained in the body to a much lesser extent than the organic forms.Two epidemiologic investigations carried out in South Dakota and in northern Italy have suggested that environmental Se species, particularly the inorganic ones, might be involved in the etiology of a severe motor neuron disease of unknown origin, sporadic amyotrophic lateral sclerosis (ALS). Veterinary medicine observations and toxicological studies have shown that some Se compounds have, in swine and in cattle, a selective toxicity to motor neurons, thus strengthening the still limited epidemiologic evidence. Furthermore, neurotoxic effects of Se species have been shown in several laboratory studies and even at very low concentrations, particularly for the inorganic species. Following Se treatment, a decrease in locomotor activity in rats, hind limb paralysis and cardiorespiratory effects in mice, and paralysis in an experimental worm model have been observed. In laboratory studies carried out using inorganic and less frequently organic Se forms in different animal species, the metalloid has been shown to interfere with several pathogenetic mechanisms potentially related to neurotoxicity, such as inhibition of prostaglandin D synthase in the brain, inhibition of squalene monooxigenase with potential cholesterol synthesis abnormalities, peripheral segmental demelination, and paralysis, increase in dopamine and its metabolies, inhibition of succinic dehydrogenase, acetylcholine esterase and Na+/K+ ATPase, and induction of seizures. Se has also been shown to induce toxic effects in rabbit vascular muscle, in rat heart muscle and in chick muscle, and in addition to inhibit axonal conduction and excitatory postsynaptic potentials, indicating the capacity of this metalloid to alter both nervous and muscle functions.Overall, these findings from the epidemiologic and the toxicological literature indicate that environmental Se, particularly when occurring in its inorganic forms in drinking waters or occupational settings, might be a risk factor for ALS, suggesting the opportunity to further investigate this issue
Health effects of environmental exposure to electromagnetic fields in Reggio Emilia, northern Italy
No full textObjective: Environmental exposure to electromagnetic fields has been suggested to increase the risk of acute lymphoblastic leukemia, particularly in children, amyotrophiclateral sclerosis and birth defects. We aimed at analyzing the risk of these diseases in a population residing near highvoltagepower lines.Material and methods: We identified all cases of acute lymphoblastic leukemia, amyotrophic lateral sclerosis and birth defects diagnosed between 1986 and 2005, from 1996 to 2005 and from 1998 to 2005, respectively, in the population of Reggio Emilia, northern Italy (around 140,000 inhabitants).We then examined the life-time residential history of thesepatients (or their mothers for congenital anomalies), as well as of age- and sex-matched population controls, to analyze whether prior residence near 4 power lines in the western part of the municipal territory, where electromagnetic fields exposure renged from 0.1 to over 0.5 μT. Results: Residence in the exposed area did notassociated with excess risk of acute lymphoblastic leukemia and amyotrophic lateral sclerosis, and of birth defects in the offspring.Conclusions: We were unable to identify adverse health effects ofelectromagnetic fields exposure in this population. Further research in a larger population exposed to electromagnetic fields is currently in progress
Evaluation of the drinking water selenium standard: an update.
No full textRecent studies suggesting a diabetogenic activity of selenium (Se) have raised concern about the human health effects of this metalloid of considerable nutritional and toxicological interest. Uncertainties exist about the adequate environmental levels of this metalloid, in particular, regarding the safe upper standard in drinking water, considering the very few epidemiologic studies carried out on this topic.We summarize results of our epidemiologic studies on long-term effects of consumption of municipal tapwater with naturally-occurring unusually high levels of Se (7-9 Âμg/l), within a non-seleniferous Italian area. Speciation analyses demonstrated that in that tapwater Se was almost entirely present in its hexavalent inorganic form, selenate. After checking for potential confounders, long-term consumers of the high-Se drinking water experienced no substantial change in overall mortality and in prevalence at birth of congenital anomalies, whilst incidence of amyotrophic lateral sclerosis and of some site-specific cancers exceeded that expected on the basis of reference rates. No beneficial effect on prostate cancer risk emerged, consistently with results of a recently published large trial carried out in the US.Our results are corroborated by laboratory studies, which demonstrated that inorganic (tetravalent) Se is toxic at concentrations as low as 0,8 Âμg/l, also confirming that toxicity of inorganic Se species far exceeds that of the organic forms.Overall, these findings indicate that current WHO drinking water upper Se standard, 10 Âμg/l, might be inadequate to protect human health, suggesting the need for additional epidemiologic studies on health effects of exposure to specific Se species through drinking water
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