1,720,972 research outputs found
Dottrine mediche e oscuramento della sperimentazione tra il XVII e il XVIII secolo
No full textPer un lungo periodo dalla costruzione dei primi microscopi composti, gli scienziati non riconobbero le potenzialità di questo strumento negli studi medici e nella diagnostica clinica. Fattori tecnici e teorici bloccarono l’impiego del microscopio nella soluzione di problemi medici. Particolarmente rilevante nel determinare questa situazione fu l’assenza di teorie mediche che richiedessero lo studio dell’organismo vivente a livello microscopico.
Solo pochi scienziati ne intuirono il valore d’uso. Fra questi, è giusto ricordare Giuseppe Campani che introdusse rilevanti miglioramenti costruttivi nel microscopio, ed illustrò con chiarezza le potenzialità dello strumento nell'analizzare ferite o lesioni cutanee direttamente sul paziente, seguendone l’evoluzione e la risposta alla terapia. Tuttavia, nonostante la chiarezza delle proposte di Campani e di altri, per più di un secolo vi fu un diffuso rigetto dell’idea di un possibile uso del microscopio per risolvere problemi di medicina. Questo generale scetticismo fu improvvisamente rimosso dopo la pubblicazione delle teorie e gli esperimenti di R.Virchow, L.Pasteur e di R.
Koch. Dopo di allora il microscopio divenne uno strumento di base indispensabile nello studio e nella diagnostica delle malattie. Recenti sviluppi delle tecnologie ottiche hanno portato all’introduzione di microscopi capaci di produrre immagini a fuoco di piani diversi e a grande risoluzione spaziale, il che permette lo studio in vivo di lesioni di superficie ai diversi piani, la loro evoluzione e gli effetti del trattamento terapeutico
Atomic force microscopy observations of acyl chains in phospholipids
No full textThe potential use of atomic force microscopy (AFM) to image the mode of assembly and to measure the corresponding lattice parameters of model systems consisting of ordered aggregates of cardiolipin molecules has been investigated. An unprecedented resolution of about 0.2 nm has been achieved on suitably prepared specimens. This enables the orientational order and the positional correlations of the individual molecules in the lattice to be defined, and submolecular details, such as the acyl chains and the polar groups, to be imaged. The structural parameters derived from AFM have been compared with those obtained by transmission electron diffraction of the same specimen and found to be in excellent agreement. AFM turns out to be a powerful, and probably a unique tool to reveal local phase variations in systems, such as biological membranes, that have non-homogeneous composition and organization
Use of the fluorescent dye 10-N-nonyl acridine orange in quantitative and location assays of cardiolipin: a study on different experimental models
No full textThe fluorescent dye 10-N-nonyl acridine orange (NAO) is extensively used for location and quantitative assays of cardiolipin in living cells on the assumption of its high specificity for cardiolipin; however, the limits and the mechanism of this specificity are not clear. Moreover, whether factors such as the membrane potential in mitochondria may limit the consistency of the results obtained by this method is open to discussion. The aim of this research was to investigate the effects of some experimental factors on the selective fluorescence of NAO in the presence of cardiolipin in artificial and natural membranes (mitochondria). The results show that the fluorescence of NAO, due to interaction with cardiolipin, is significantly modified by factors that control the spatial arrangement of cardiolipin molecules within the space of the membrane under investigation. Moreover, the present observations suggest that the specific effect of cardiolipin is to facilitate the dimerization of this fluorescent dye, thus confirming that reliable measurements of cardiolipin concentration can be obtained only when the NAO/cardiolipin molar ratio is equal to 2. The finding is also reported that in isolated respiring mitochondria the interaction of NAO with cardiolipin is somewhat related to the respiratory state of mitochondria
Effect of cardiolipin on functional properties of isolated rat liver mitochondria
No full textThe specific involvement of cardiolipin in modulating and/or controlling the activity of a number of mitochondrial carriers, enzymes and receptors is well documented; however, comparatively less understood is its role for the integrated functions of intact mitochondria. The aim of the present research was to get a better insight into this problem by investigating the effect of in vitro addition of cardiolipin on the properties of isolated liver mitochondria. The results obtained show that cardiolipin induces extensive structural and functional perturbations at the level of the inner mitochondrial membrane. In fact, addition of cardiolipin to intact mitochondria causes a significant increase of proton leak associated with a parallel increase of respiratory rate in State 4. Concomitantly, a slight uncoupling of phosphorylation associated with a moderate increase in ATPase activity is observed. Furthermore, the pore-mediated membrane permeability to calcium is drastically modified, an effect that can be reversed by addition of cyclosporin
Lipid oxidation deletes the nanodomain organization of artificial membranes
No full textNanoscopic domains with different crystal structures have been induced in closed artificial membranes and have been directly imaged by atomic force microscopy at a spatial resolution better than 0.3 nm. These observations provide experimental evidence to the hydrophobic mismatching theory of lateral phase separation phenomena. Under oxidant conditions, the lipid-lipid assembly reorganises into a new steady-state structure with disappearance of specific nanodomains. This finding may contribute to understanding the mechanism of peroxidative damage to membrane properties. In fact, alterations of specific anodes of molecular conformation and packing may lead to perturbation of specific properties
Giuseppe Moscati: a man, a physician and a scientist
Full text linkThe life of Giuseppe Moscati (1880-1927) as a man, as a physician and as a scientist may be framed within the cultural climate of Positivism, which spread over the last years of the 19th century and the beginning of the 20th Century. His activity contributed to patients' care improvement; in addition to meticulous drug regimens, he also prescribed a methodology of spiritual care, involving meditation and self-control as part of an holistic approach to healthcare. Our review deals with his published researches, highlighting the innovative findings on the juvenile diabetes treatment and extensive clinical changes consequent upon nephritis. This extraordinary man put considerable emphasis on primary care and holistic health in Italy, pioneering a new patient-centred, and holistic approach to medicine
Atomic Force Microscopy: a modern technique in Membrane Science
No full textAtomic force microscopy: a modern versatile technique in membrane scienc
In vitro 1H and 31P NMR spectroscopy as a tool for investigating muscle energy state in facioscapulohumeral muscolar dystrophy (FSHD) mouse model
No full textFacioscapulohumeral muscular dystrophy (FSHD) is a hereditary neuromuscular disorder characterized by progressive weakness and atrophy of the facial, shoulder, abdominal and pelvic girdle muscles. We proposed that its pathogenesis could be associated with the over-expression of genes mapped at chromosome 4q35, ANT1, FRG1 and FRG2. Consistently, transgenic mice over-expressing FRG1 develop a progressive muscular dystrophy characterized by symptoms similar to those of human disease and thus it can be considered a reliable mice model to study FSHD. FSHD mouse model shows reduced tolerance to exercise and muscle weakness which can be related to disorders of muscle energy mechanisms.To investigate this hypothesis we have applied 1H and 31P NMR spectroscopy to wild-type and dystrophic vastus muscle PCA extracts to evaluate the muscle energy parameters by measuring the concentration of the major energy metabolites (ATP, ADP, AMP, Pi, Cr and PCr
Interaction of carnitine with mitochondrial cardiolipin
No full textThe physiological role of L-carnitine is to determine the transport of acyl-CoA through the mitochondrial membrane. However, some observations may also suggest a direct effect of the molecule per se on the physical properties of the membrane, most probably at the level of the binding site. This possibility has been investigated by studying the influence of adriamycin, a drug that binds to cardiolipin, on the effect of carnitine on isolated rat liver mitochondria. It has been found that adriamycin almost abolishes the activating effect of carnitine on state 2 respiration. The effect and its inhibition is seen by using either the L-form of carnitine or the D-form or both. Cardiolipin removes the effect of adriamycin and restores the activation by carnitine. It is proposed that some effects of carnitine on mitochondrial properties may be the result of interaction of carnitine with cardiolipin at the membrane level
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