119 research outputs found
Exocrine gastric secretion and gastritis: pathophysiological and clinical relationships.
No full textGastric exocrine secretion, both acid and non-acid, is required for micronutrients absorption, such as iron, calcium and vitamin B12, drugs absorption, protein digestion. Clinical presentation of a gastric secretion impairment might be then characterized by the presence of both gastrointestinal and non-gastrointestinal specific symptoms (i.e. anemia) or to a non-response to therapies. The main factor that impairs gastric exocrine secretion homeostasis is mucosal chronic inflammation that principally occurs after colonization by Helicobacter pylori (Hp). The extent and distribution of gastritis ultimately determine the clinical outcome linked to differences in gastric acid secretion status, the involvement of gastric body leading to a decrease in gastric exocrine secretion with possible progression to mucosal atrophy towards cancer. A correct clinical strategy in the management of Hp infected patients should be then to early identify body involvement, a diagnosis generally missed in that body biopsies are not routinely performed. The use of gastric serological markers, gastrin and pepsinogens, are helpful in suspecting the presence of mucosal atrophy but their diagnostic accuracy for non-atrophic chronic gastritis topography is not adequate despite a good specificity due to the low sensitivity, of all the available biomarkers. Gastric serology associated to anemia/iron-deficiency screening might nevertheless been helpful in the framing of patients that undergo endoscopy in order to highlight the need of extensive mucosal biopsies sampling
Comunicazione cellulare, livelli e strutture ordinate.
No full textLe cellule interagiscono per formare strutture di ordine superiorecome colonie monoclonali o tessuti cellulari. Le Reti Booleane Casuali (RBN)possono essere considerate come modello di una cellula isolata ed è dunque diestrema importanza l’analisi della relazione tra la dinamica di una singola RBNe quella di un insieme di reti interagenti. Presentiamo un modello adatto alloscopo: un automa cellulare bidimensionale in cui ogni cella è occupata da unaRBN. Il meccanismo di interazione tra le reti dell’automa è ispirato allacomunicazione intercellulare. L’analisi dello stato di ordine del modello puòavvenire al livello dell’automa e a quello della singola rete costituente. Siosserva che l’influenza della forza di interazione sul grado di ordine delle RBNnon è univoca, in alcuni casi l’ordine è accresciuto, mentre in altri è amplificatoil disordine. Sono state individuate tre tipologie di comportamento, al cresceredell’intensità dell’interazione, che appaiono correlate alla dinamica dellaspecifica RBN in assenza di interazione
COMUNICAZIONE CELLULARE, LIVELLI E STRUTTURE ORDINATE
No full textLe cellule interagiscono per formare strutture di ordine superiore come colonie monoclonali o tessuti cellulari. Le Reti Booleane Casuali (RBN) possono essere considerate come modello di una cellula isolata ed è dunque di estrema importanza l’analisi della relazione tra la dinamica di una singola RBN e quella di un insieme di reti interagenti. Presentiamo un modello adatto allo scopo: un automa cellulare bidimensionale in cui ogni cella è occupata da una RBN. Il meccanismo di interazione tra le reti dell’automa è ispirato alla comunicazione intercellulare. L’analisi dello stato di ordine del modello può avvenire al livello dell’automa e a quello della singola rete costituente. Si osserva che l’influenza della forza di interazione sul grado di ordine delle RBN non è univoca, in alcuni casi l’ordine è accresciuto, mentre in altri è amplificato il disordine. Sono state individuate tre tipologie di comportamento, al crescere dell’intensità dell’interazione, che appaiono correlate alla dinamica della specifica RBN in assenza di interazione
Valanghe in reti booleane a topologia scale-free
No full textL'articolo tratta della simulazione di eventi di knock-out tramite reti booleane con topologia scale-free, e del confronto dei risultati con dati reali (eventi in Saccaromicies Cerevisiae
Addressing Immune Response Dysfunction in an Integrated Approach for Testing and Assessment for Non-Genotoxic Carcinogens in Humans: A Targeted Analysis
Get PDFMost known chemical carcinogens induce the direct activation of DNA damage, either directly or following metabolic activation. However, carcinogens do not always operate directly through genotoxic mechanisms but can do so via non-genotoxic carcinogenic (NGTxC) mechanisms. Immune dysfunction is one of these key events that NGTxCs have been shown to modify. The immune system is a first line of defence against transformed cells, with an innate immune response against cancer cells and mechanisms of immune evasion. Here, we review the key events of immune dysfunction. These include immunotoxicity, immune evasion, immune suppression and inflammatory-mediated immune responses, and the key players in the molecular disruption of immune anti-cancer molecular signalling pathways, particularly those mediated by cytokines and the Aryl hydrocarbon Receptor, in relation to the identification of NGTxC. The plasticity of cytokines towards functional flexibility in response to environmental stressors is also discussed from an evolutionary heritage perspective. This is combined with a critical assessment of the suitability for the regulatory application of currently available test method tools and is corroborated by the key biomarkers of, e.g., MAPK, mTOR, PD-L1, TIL and Tregs, CD8+, FoxP3+, WNT, IL-17, IL-11, IL-10, and TNF alpha, as identified from robust cancer biopsy studies. Finally, an understanding of how to address these endpoints for chemical hazard regulatory purposes, within an integrated approach to testing and assessment for NGTxC, is proposed
Differential equations and cellular automata models of the growth of cell cultures and transformation foci
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A cellular automata model for the simulation of in vitro carcinogenesis tests
No full textIn vitro tests are very powerful methods to assess the carcinogenic effects of different substances and to study the initial phases of tumor development. A CA model of the formation of transformation foci in cell cultures which are exposed to a carcinogen is presented here, based on known facts about carcinogenesis and about reasonable assumptions, which gives rise to a cell growth dynamics similar to the one experimentally observed. The model can be used to test formal hypotheses about different interfering phenomena and about their relative strengt
The use of a physiologically based pharmacokinetic modelling in a “full-chain” exposure assessment framework: A case study on urban and industrial pollution in northern italy
Get PDFBackground and goals: The estimate of the internal dose provided by physiologically based pharmacokinetic (PBPK) modelling is a big step forward in the frame of human health risk assessment (HRA) from contaminating sources. The PBPK model included in the MERLIN-Expo platform was here tested with data collected in a human biomonitoring (HBM) pilot study to check model efficacy in predicting concentrations in human blood and urine of people exposed to a modern solid waste incinerator (SWI). The aim of the study was to investigate if the use of a PBPK model integrated in a computational platform could replace more expensive and invasive pilot studies. Twenty eight subjects living and working within 4 km of the incinerator (exposed) and 21 subjects living and working outside this area (unexposed) were selected among the population recruited in the HBM study. The group of exposed (E) subjects and the group of non-exposed (NE) subjects were comparable for all relevant anthropometric characteristics and exposure parameters except for the exposure to SWI emissions. Three different scenarios were created: an “only diet-scenario” (DS), a “worst case scenario” (WCS) and a “most likely scenario” (MLS). The platform was tested for blood-lead (B-Pb), urinary-lead (U-Pb), urinary-anthracene (U-Ant) and urinary-fluoranthene (U-Flt). Average estimated U-Pb was statistically equal to the measured one (est. 0.411~0.278; meas. 0.398~0.455 μg/L) and estimated vs. measured U-Ant differ by one order of magnitude only (est. 0.018~0.010; meas. 0.537~0.444 ng/L) while for U-Flt and B-Pb, the error was respectively of two and four orders of magnitude. It is likely that the extremely high accuracy in the Pb concentration input values referring to diet led to the very accurate estimate for this chemical in urine, but the higher error in the B-Pb computed value suggests that PBPK model equations cannot entirely capture the dynamics for blood compartments. MERLIN-Expo seems a very promising tool in saving time, energy and money in the screening step of the HRA framework; however, many software validations are still required
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