This article is an educational review about the fundamental aspects related to the proposal of the existence of a peripheral sympathetic reflex regulated by histamine, through its effect on ...presynaptic H3 type receptors, under the interaction of a sensory neuron that would be mediated by Substance P. In this respect, we consider it useful to highlight the role of histamine, so we discuss some aspects about its history, metabolism, and function, as well as its interaction with H3 type receptors that are considered as neuroreceptors, which define and typify it as a neuromediator at both levels of the nervous system, central and peripheral.
The increasing use of oxide nanoparticles (NPs) in commercial products has intensified the potential release into the aquatic environment where algae represent the basis of the trophic chain. NP ...effects upon algae population growth were indeed already reported in literature, but the concurrent effects at cellular and genomic levels are still largely unexplored.
Our work investigates the genotoxic (by COMET assay) and cytotoxic effects (by qualitative ROS production and cell viability) of ZnO nanoparticles toward marine microalgae Dunaliella tertiolecta. A comparison at defined population growth inhibition levels (i.e. 50% Effect Concentration, EC50, and No Observed Effect Concentration, NOEC) with SiO2 and TiO2 genotoxic effects and previously investigated cytotoxic effects (Manzo et al., 2015) was performed in order to elucidate the possible diverse mechanisms leading to algae growth inhibition.
After 72h exposure, ZnO particles act firstly at the level of cell division inhibition (EC50: 2mg Zn/L) while the genotoxic action is evident only starting from 5mg Zn/L. This outcome could be ascribable mainly to the release of toxic ions from the aggregate of ZnO particle in the proximity of cell membrane.
In the main, at EC50 and NOEC values for ZnO NPs showed the lowest cytotoxic and genotoxic effect with respect to TiO2 and SiO2. Based on Mutagenic Index (MI) the rank of toxicity is actually: TiO2>SiO2>ZnO with TiO2 and SiO2 that showed similar MI values at both NOEC and EC50 concentrations.
The results presented herein suggest that up to TiO2 NOEC (7.5mg/L), the algae DNA repair mechanism is efficient and the DNA damage does not result in an evident algae population growth inhibition. A similar trend for SiO2, although at lower effect level with respect to TiO2, is observable.
The comparison among all the tested nanomaterial toxicity patterns highlighted that the algae population growth inhibition occurred through pathways specific for each NP also related to their different physicochemical behaviors in seawater.
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•ZnO (nano) particles act firstly at level of cell division inhibition.•ZnO genotoxic action is evident only starting from 5mg Zn/L.•The ZnO toxicity can be due mainly but not solely to the release of toxic ions.•At algae NOEC and EC50 the rank of genotoxicity is: TiO2>SiO2>ZnO.•SiO2 and TiO2 show different pathways leading to algae population growth inhibition.
In this study, the change of electrochemical parameters during the gradual water accumulation of a polymer electrolyte fuel cell (PEFC) are estimated using electrochemical impedance spectroscopy ...(EIS) measurements and an impedance model based on electrode theory during a two‐step oxygen reduction reaction (ORR). EIS measurements were carried out in a 5 cm2 H2/O2 PEFC operated under a dead‐ended configuration of the gas reactants and during gradual accumulation of water. Kramers‐Kronig evaluation demonstrated that the EIS measurements comply with stability and linearity properties and the inductive loops featured at low frequencies are attributed to electrochemical mechanisms within the PEFC and not to instability during gradual water accumulation. The impedance model has been reported in a previous study and simulates inductive loops at low frequencies which are attributed to platinum oxide formation during the ORR. The estimated parameters obtained from this EIS‐modeling analysis can provide an insight into the decrease in PEFC performance during flooding conditions. A further qualitative analysis considering the effect of long‐term water accumulation on the oxygen‐reduction charge transfer resistance is discussed. It is possible to have an insight into the physical mechanisms of the PEFC, by combining different experimental techniques and fundamental theory in a complimentary manner.
In the last years, applications for silver nanoparticles (Ag NPs) continue to increase together with the concerns about their potential input and hazards in aquatic ecosystems, where microalgae are ...key organisms. The aim of the present study was to assess the relative sensitivity of three marine microalgae species with differences in cell wall composition/structure exposed to Poly N-vinyl-2-pirrolidone/Polyethyleneimine (PVP/PEI) coated 5nm Ag NPs and uncoated 47nm Ag NP. As limited attention has been paid to the role of coating agents in NP toxicity, the effect of PVP/PEI alone was also evaluated. After 72h in artificial seawater, 47nm Ag NPs formed around 1400nm size aggregates while PVP/PEI coated 5nm Ag NPs reached around 90nm. Ag+ release in seawater was around 3% for 47nm Ag NPs and 30% for PVP/PEI coated 5nm Ag NPs. PVP/PEI coated 5nm Ag NP aggregates entrapped the algal cells in a network of heteroaggregates, while uncoated 47nm Ag NPs interacted to a lesser extent with algae. The concentration of PVP/PEI coated 5nm Ag NPs that exerted the median effect (EC50) on algae growth pointed out differences in algae sensitivity: T. suecica was about 10 times more sensitive than I. galbana and P. tricornutum. Further, the coating agent alone was as toxic to algae as PVP/PEI coated 5nm Ag NPs, suggesting that presence of the coating agent was the main driver of toxicity of coated NPs. Uncoated 47nm Ag NPs instead, showed similar toxicity towards algae although P. tricornutum was slightly less sensitive than T. suecica and I. galbana, which agrees with the presence of a resistant silicified cell wall in the diatom. The present work demonstrates differences in sensitivity of three marine microalgae, possibly related to their cell surface and size characteristics.
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•Effects of coated, uncoated Ag NPs and coating agent on microalgae were evaluated.•Coated 5 nm Ag NPs produced aggregates of smaller size and released 10 times more Ag ions than uncoated 47 nm Ag NPs.•Coated 5 nm Ag NPs were more toxic than uncoated 47 nm Ag NPs.•The coating agent alone was as toxic as coated 5 nm Ag NPs.•Tetraselmis suecica was about 10 times more sensitive than Isochrysis galbana and Phaeodactylum tricornutum.
Nanoparticles (NPs) are widely used in many industrial applications. NP fate and behavior in seawater are a very important issue for the assessment of their environmental impact and potential ...toxicity. In this study, the toxic effects of two nanomaterials, silicon dioxide (SiO
2
) and titanium dioxide (TiO
2
) NPs with similar primary size (~20 nm), on marine microalgae
Dunaliella tertiolecta
were investigated and compared. The dispersion behavior of SiO
2
and TiO
2
NPs in seawater matrix was investigated together with the relative trend of the exposed algal population growth. SiO
2
aggregates rapidly reached a constant size (600 nm) irrespective of the concentration while TiO
2
NP aggregates grew up to 4 ± 5 μm. The dose–response curve and population growth rate alteration of marine alga
D. tertiolecta
were evaluated showing that the algal population was clearly affected by the presence of TiO
2
NPs. These particles showed effects on 50 % of the population at 24.10 19.38–25.43 mg L
−1
(EC50) and a no observed effect concentration (NOEC) at 7.5 mg L
−1
. The 1 % effect concentration (EC1) value was nearly above the actual estimated environmental concentration in the aquatic environment. SiO
2
NPs were less toxic than TiO
2
for
D. tertiolecta
, with EC50 and NOEC values one order of magnitude higher. The overall toxic action seemed due to the contact between aggregates and cell surfaces, but while for SiO
2
a direct action upon membrane integrity could be observed after the third day of exposure, TiO
2
seemed to exert its toxic action in the first hours of exposure, mostly via cell entrapment and agglomeration.
Antibiotic tolerance is typically associated with a phenotypic change within a bacterial population, resulting in a transient decrease in antibiotic susceptibility that can contribute to treatment ...failure and recurrent infections. Although tolerant cells may emerge prior to treatment, the stress of prolonged antibiotic exposure can also promote tolerance. Here, we sought to determine how Yersinia pseudotuberculosis responds to doxycycline exposure, to then verify if these gene expression changes could promote doxycycline tolerance in culture and in our mouse model of infection. Only four genes were differentially regulated in response to a physiologically-relevant dose of doxycycline: osmB and ompF were upregulated, tusB and cnfy were downregulated; differential expression also occurred during doxycycline treatment in the mouse. ompF, tusB and cnfy were also differentially regulated in response to chloramphenicol, indicating these could be general responses to ribosomal inhibition. cnfy has previously been associated with persistence and was not a major focus here. We found deletion of the OmpF porin resulted in increased antibiotic accumulation, suggesting expression may promote diffusion of doxycycline out of the cell, while OsmB lipoprotein had a minor impact on antibiotic permeability. Overexpression of tusB significantly impaired bacterial survival in culture and in the mouse, suggesting that tRNA modification by tusB, and the resulting impacts on translational machinery, promotes survival during treatment with an antibiotic classically viewed as bacteriostatic. We believe this may be the first observation of bactericidal activity of doxycycline under physiological conditions, which was revealed by reversing tusB downregulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Giardiasis is a worldwide parasitic disease that affects mainly children and immunosuppressed people. Side effects and the emergence of resistance over current used drugs make imperative looking for ...new antiparasitics through discovering of new biological targets and designing of novel drugs. Recently, it has determined that gastric proton-pump inhibitors (PPI) have anti-giardiasic activity. The glycolytic enzyme, triosephosphate isomerase (GlTIM), is one of its potential targets. Therefore, we employed the scaffold of PPI to design new compounds aimed to increase their antigiardial capacity by inactivating GlTIM. Here we demonstrated that two novel PPI-derivatives (BHO2 and BHO3), have better anti-giardiasic activity than omeprazole in concentrations around 120-130 µM, without cytotoxic effect on mammal cell cultures. The derivatives inactivated GlTIM through the chemical modification of Cys222 promoting local structural changes in the enzyme. Furthermore, derivatives forms adducts linked to Cys residues through a C-S bond. We demonstrated that PPI can be used as scaffolds to design better antiparasitic molecules; we also are proposing a molecular mechanism of reaction for these novel derivatives.
Aging is a physiological decline process. The number of older adults is growing around the world; therefore, the incidence of cognitive impairment, dementia, and other diseases related to aging ...increases. The main cellular factors that converge in the aging process are mitochondrial dysfunction, antioxidant impairment, inflammation, and immune response decline, among others. In this context, these cellular changes have an influence on the kynurenine pathway (KP), the main route of tryptophan (Trp) catabolism. KP metabolites have been involved in the aging process and neurodegenerative diseases. Although there are changes in the metabolite levels with age, at this time, there is no study that has evaluated cognitive decline as a consequence of Trp catabolism fluctuation in aging. The aim of this study was to evaluate the relation between the changes in Trp catabolism and cognitive impairment associated with age through KP metabolites level alterations in women over 50 years of age. Seventy-seven nondemented women over 50 years old were examined with a standardized cognitive screening evaluation in Spanish language (Neuropsi), Beck anxiety inventory (BAI), and the geriatric depression scale (GDS). Also, serum levels of Trp, kynurenine (Kyn), kynurenic acid (KYNA), and 3-hydroykynurenine (3-HK) and the glutathione ratio (GSH/GSSG) were measured. Results showed a negative correlation between age and Trp levels and a positive correlation between age and KYNA/Trp and 3-HK/Trp ratios. The level of cognitive impairment showed a significant positive association with age and with kynurenine pathway activation and a significant negative correlation with Trp levels. The GSH/GSSG ratio correlated positively with Trp levels and negatively with Kyn/Trp and 3-HK/Trp ratios. The depression score correlated negatively with Trp and positively with the 3-HK/Trp ratio. We concluded that KP activation increases with age and it is strongly associated with the level of cognition performance in nondemented women over 50 years of age.
Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in USA, and 10–20% of patients will develop persistent symptoms despite treatment (“post-treatment Lyme disease ...syndrome”). B. burgdorferi persisters, which are not killed by the current antibiotics for Lyme disease, are considered one possible cause. Disulfiram has shown to be active against B. burgdorferi, but its activity against persistent forms is not well characterized. We assessed disulfiram as single drug and in combinations against stationary-phase B. burgdorferi culture enriched with persisters. Disulfiram was not very effective in the drug exposure experiment (survival rate (SR) 46.3%) or in combinations. Clarithromycin (SR 41.1%) and nitroxoline (SR 37.5%) were equally effective when compared to the current Lyme antibiotic cefuroxime (SR 36.8%) and more active than disulfiram. Cefuroxime + clarithromycin (SR 25.9%) and cefuroxime + nitroxoline (SR 27.5%) were significantly more active than cefuroxime + disulfiram (SR 41.7%). When replacing disulfiram with clarithromycin or nitroxoline in three-drug combinations, bacterial viability decreased significantly and subculture studies showed that combinations with these two drugs (cefuroxime + clarithromycin/nitroxoline + furazolidone/nitazoxanide) inhibited the regrowth, while disulfiram combinations did not (cefuroxime + disulfiram + furazolidone/nitazoxanide). Thus, clarithromycin and nitroxoline should be further assessed to determine their role as potential treatment alternatives in the future.
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