243 research outputs found
Effetti osservati sulla salute umana.
No full textSono stati riportati in letteratura una serie di case report e di casi aneddotici che descrivono effetti avversi sulla salute umana attribuiti al gruppo delle palitossine (PLTX) e/o ad alcuni analoghi strutturali, a seguito di esposizioni attraverso varie vie. I segni e sintomi registrati indicano l’insorgenza di effetti locali al sito di contatto, generalmente riconducibili a reazioni di carattere irritativo e infiammatorio, ai quali in alcuni casi si aggiunge una sintomatologia sistemica. Gli scenari espositivi più rilevanti associati ad attività ricreative prevedono un contatto diretto durante la balneazione, attraverso la cute e le mucose, con le tossine disciolte in acqua e/o con le specie algali produttrici. Alcune segnalazioni di effetti avversi su addetti e hobbisti coinvolti nella pulizia di acquari e il ritrovamento di livelli non trascurabili di PLTX in coralli da acquario indicano che anche tali categorie sono da considerarsi a rischio. L’altro scenario da considerare prevede l’inalazione di aerosol di acqua marina durante fioriture di Ostreopsis spp., prodotto a seguito di movimenti forzati dell’acqua marina per specifiche attività (es. nel caso di attività sportive in acque contaminate) e/o in concomitanza di condizioni meteoclimatiche favorevoli (es. vento forte e mareggiate). Quest’ultima via di esposizione coinvolge quindi non solo i ‘bagnanti’ propriamente detti ma anche soggetti che sostano in prossimità della spiaggia e/o sul lungomare.
A queste vie di esposizione si aggiunge quella orale, associata sia all’ingestione involontaria di acqua durante attività ricreative (es. durante il nuoto) che al consumo di prodotti ittici contaminati. Le PLTX possono, infatti, accumularsi nei molluschi marini eduli, nei crostacei e nei pesci: sindromi di avvelenamento talvolta letali, note col nome di clupeotoxismo, sono state descritte in regioni tropicali anche se spesso l’identificazione della tossina è risultata incompleta o mancante e, in questi casi, l’attribuzione dell’avvelenamento all’ingestione di PLTX (relazione causa-effetto) è stata fatta sulla base del quadro clinico, dell’anamnesi e dell’ingestione di alimenti di origine marina. Nonostante alcuni prodotti ittici, quali sardine, acciughe e granchi, parte integrante della dieta mediterranea, possano accumulare PLTX in alte concentrazioni e rappresentino quindi l’anello della catena alimentare attraverso cui l’uomo è potenzialmente esposto, finora non sono stati riportati nel bacino del Mediterraneo effetti associati all’ingestione di prodotti ittici contaminati dalle tossine prodotte da Ostreopsis cf. ovata
In vitro effects of polyhalogenated hydrocarbons on liver mitochondria respiration and microsomal cytochrome P-450
No full textThe present study evidenced the critical levels of six major polyhalogenated hydrocarbons (PHH's), namely chloroform, carbon tetrachloride, 1,1,1-trichloroethane, 1,2-dibromoethane,perchloroethylene, hexachlorobutadiene, over which significant inhibitory effects of the mitochondrial respiratory chain take place in vitro. At these critical levels, even in PB-induced animals only a very little fraction of cytochrome P-450 is saturated by the compounds and therefore the microsomal metabolism plays no effective role either in decreasing the levels of the test chemicals under the threshold of clear direct adverse effects in mitochondria, nor to the formation of toxic metabolites. Our data show also that phenobarbital not only enhances both the direct and metabolism-mediated interaction of most tested PHH with microsomal cytochrome P-450, but also increases the affinity of hexachlorobutadiene, chloroform and carbon tetrachloride for the mitochondrial sites resulting in respiration inhibition
QT Prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary screening of torsadogenicity of drugs and drug
No full textFlavonoids as new regulators of mitochondrial potassium channels: contribution to cardioprotection
No full textObjectives Acute myocardial ischemia is one of the major causes of illness in western society. Reduced coronary blood supply leads to cell death and loss of cardiomyocyte population, resulting in serious and often irreversible consequences on myocardial function. Mitochondrial potassium (mitoK) channels have been identified as fine regulators of mitochondrial function and, consequently, in the metabolism of the whole cell, and in the mechanisms underlying the cardioprotection. Interestingly, mitoK channels represent a novel putative target for treating cardiovascular diseases, particularly myocardial infarction, and their modulators represent an interesting tool for pharmacological intervention. In this review, we took up the challenge of selecting flavonoids that show cardioprotective properties through the activation of mitoK channels. Key findings A brief overview of the main information on mitoK channels and their participation in the induction of cytoprotective processes was provided. Then, naringenin, quercetin, morin, theaflavin, baicalein, epigallocatechin gallate, genistein, puerarin, luteolin and proanthocyanidins demonstrated to be effective modulators of mitoK channels activity, mediating many beneficial effects. The pathophysiological role of mitoK channels has been investigated as well as the impact of flavonoids on this target with particular attention to their potential role in the prevention of cardiovascular disorders
Image_1_A Nutraceutical Strategy to Slowing Down the Progression of Cone Death in an Animal Model of Retinitis Pigmentosa.pdf
No full textRetinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by progressive degeneration of the visual cells and abnormalities in retinal pigment epithelium, the vision is lost slowly, and the final outcome is total blindness. RP primarily affects rods, but cones can also be affected as a secondary effect. Photoreceptor cell death is usually triggered by apoptosis, however the molecular mechanisms linking the rod degeneration to the secondary cone death are poorly understood. Possible causes of the secondary cone death are oxidative stress and/ or the release of toxic factors from dying rods. The aim of this study is to analyze the effect of nutraceutical molecules with antioxidant properties, on the progression of the disease in an established animal model of RP, and rd10 mice. We show that chronic treatment per os with a flavanone (naringenin) or a flavonol (quercetin) present in citrus fruits, grapes and apples, preserves retinal morphology, and ameliorates functionality. These actions are associated with a significant reduction of stress-oxidative markers, such as the detoxifying enzymes Sod1 and Sod2. In addition, naringenin and quercetin treatment reduces the levels of acrolein staining associated with a reduction of ROS in the cellular environment. The study demonstrates the beneficial effects of naringenin and quercetin, two molecules that possess antioxidant properties, limiting neurodegeneration, and thus preventing cone damage.</p
Nauji skirstinių simetriškumo testai /
No full textA new class of the tests for symmetry of random variables is considered. This class is based on the empirical characteristic function. Tests from this class are compared with the classical Sign test using graphical display of P values. It is easy to extend this approach to the multivariate case
Caco-2/tc7 cell line characterization for intestinal absorption : how reliable is this in vitro model for the prediction of the oral dose fraction absorbed in human?
No full textCaco-2 cell line is one of the most used in vitro model to study intestinal absorption of compounds at screening level. Several clones have been isolated from Caco-2 cell line and characterized for their activities. Among them, TC7 clone was isolated from a late passage of the parental Caco-2 line and has shown to consist of a more homogeneous population with respect to the most representative functions of the small intestinal enterocytes, with more developed intercellular junctions. On the basis of these characteristics, it was selected within the framework of the EU A-Cute-Tox project to check its suitability to predict intestinal transport.
In the present study, drugs, synthetic or natural chemicals have been characterized for their absorption profile in TC7 cells cultivated on semi-permeable filters for 21 days. The absorption experiments have been performed with the highest nontoxic concentration as determined in a preliminary set of cytotoxicity tests. The apparent permeability coefficient (P-app) has been extrapolated by calculating the passage of the test compound from the donor to the receiver compartment as a time function. The samples have been collected at different time intervals and the concentration of the test compounds analyzed by analytical methods (HPLC, GC, GC/MS). The P-app obtained with the TC7 clone are comparable to those obtained with the parental cell line. However, some drawbacks related to the experimental system have been highlighted (i.e. low mass balance, adsorption to the plastics), on the basis of which some compounds were excluded from the analysis.
In order to check the predictability of the model, a regression analysis has been performed by plotting P-app values vs. the fraction absorbed in humans (FA, expressed as % of the administered dose). Additional elaborations have highlighted that the specific absorption pathway (passive, active and carrier-mediated) and other factors (i.e. efflux proteins and/or metabolic activity) can strongly affect the robustness of the prediction model.
On the basis of the obtained results, TC7 clone has shown to be a model for passive diffusion as reliable as the parental cell line. However, we have remarked the non-suitability of the TC7 cells to predict intestinal absorption: (i) for highly lipophilic compounds; (ii) for poorly absorbed compounds; or (iii) when transporter-mediated routes and/or first pass metabolism are involved. The preliminary study of those factors likely influencing compound biokinetics, as well as the characterization of the cellular model with respect to metabolic and transporter competence, would help in the interpretation of data
Synthesis and B-bloking activity of(R,S)-(E)-oxmeethers of 2,3-dihydro-1,8-naphthyridine and 2,3-dihydrothiopyrano[2,3-b]pyridine: identification of B3-antagonists
No full text- …
