169,789 research outputs found
Compliance o aderenza: uno strumento essenziale per l’efficacia terapeutica
No full textDrugs don’t work in patients who don’t take them. — C. Everett Koop
L’efficacia e la tollerabilità di un trattamento farmacologico vengono valutate attraverso studi sperimentali (trial clinici), disegnati per analizzare la relazione tra la somministrazione di un farmaco e gli esiti clinici associati. Questi studi sono anche organizzati in modo che siano attuate le condizioni di trattamento più adeguate perché si possa mettere in evidenza l’effetto terapeutico desiderato. Nel trattamento dell'ipertensione arteriosa, ad esempio, queste condizioni sono rappresentate dal dosaggio, dalla durata e dalla continuità del trattamento considerato.
Stimare il grado di osservanza al trattamento da parte del paziente non è stato sempre considerato di primaria importanza al momento dell’impostazione di un trial clinico. L’accertamento della compliance terapeutica, intesa come aderenza del paziente alla terapia nella durata e nel dosaggio prescritto dal medico curante, rappresenta oggi una condizione necessaria per la verifica del raggiungimento degli esiti previsti. La rilevanza clinica dei risultati di uno studio dovrebbe essere giudicata sulla base dell’effettiva influenza che essi avranno nel modificare la pratica clinica reale. L’efficacia sperimentale attesa (efficacy) è la capacità di un trattamento di modificare in maniera positiva il decorso di una malattia, in condizioni organizzative migliori di quelle della pratica quotidiana. L’efficacia nella pratica (effectiveness) è il beneficio che un trattamento mostra durante la sua applicazione nelle condizioni di pratica clinica corrente, di solito con minore controllo dell’aderenza e peggiori condizioni organizzative di quelle proprie di uno studio sperimentale. Negli ultimi anni, è emerso che il grado di compliance al trattamento rappresenta una variabile molto importante nel determinare differenze tra gli esiti clinici riscontrati durante i trials clinici e la pratica clinica quotidiana.
Ciò ha incentivato lo sviluppo di studi volti ad una valutazione quantitativa dei processi che realmente avvengono nella pratica clinica e dei risultati di efficacia terapeutica che da essi ne derivano. Rilevare e quantificare l’aderenza dei pazienti alla terapia negli studi clinici è di grande valore al fine di ottenere risultati di efficacia altamente generalizzabili, in quanto si riferiscono ai pazienti che hanno effettivamente portato a termine la sperimentazione in rapporto a quanti hanno abbandonato la terapia nel corso dello studio. L’analisi di questo fenomeno ha assunto una rilevante importanza perché può ridimensionare l'efficacia complessiva finale di uno schema terapeutico e, anche, metterne in dubbio l’applicabilità futura
A not cytotoxic nickel concentration alters the expression of neuronal differentiation markers in NT2 cells
No full textNickel, a known occupational/environmental hazard, may cross the placenta and reach appreciable concentrations in various fetal organs, including the brain. The aim of this study was to investigate whether nickel interferes with the process of neuronal differentiation.
Following a 4 week treatment with retinoic acid (10 μM), the human teratocarcinoma-derived NTera2/D1 cell line (NT2 cells) terminally differentiate into neurons which recapitulate many features of human fetal neurons. The continuous exposure of the differentiating NT2 cells to a not cytotoxic nickel concentration (10 μM) increased the expression of specific neuronal differentiation markers such as Neural Cell Adhesion Molecule (NCAM) and Microtubule Associated Protein 2 (MAP2). Furthermore, nickel exposure increased the expression of Hypoxia-Inducible-Factor-1α (HIF-1α) and induced the activation of the AKT/PKB kinase pathway, as shown by the increase of P(Ser-9)-GSK-3β, the inactive form of glycogen synthase kinase-3β (GSK-3β). Intriguingly, by the end of the fourth week the expression of tyrosine hydroxylase (TH) protein, a marker of dopaminergic neurons, was lower in nickel-treated than in control cultures. Thus, likely by partially mimicking hypoxic conditions, a not-cytotoxic nickel concentration appears to alter the process of neuronal differentiation and hinder the expression of the dopaminergic neuronal phenotype. Taken together, these results suggest that nickel, by altering normal brain development, may increase susceptibility to neuro-psychopathology later in life
"Microsfere di idrogeli di polimeri polisaccaridici contenenti cellule neurali secernenti dopamina, procedimento per la /01'0 preparazione e loro usi in campo medico"
No full textLa presente invenzione concerne microsfere di idrogeli di polimeri polisaccaridici contenenti cellule neurali secernenti dopamina, procedimento per la loro preparazione e loro usi in campo medico
Neuro-differentiated Ntera2 cancer stem cells encapsulated in alginate beads: first evidence of biological functionality
No full textThe present communication investigates an application of alginate encapsulation technology to the differentiation of the embryonic cancer stem NTera2 cells (NT2) into dopamine-producing cells. the encapsulation of cells in polymeric beads allows their immune isolation and makes them eligible for transplantation, thus representing a promising biotech tool for the delivery of biologically active compounds to the brain. the polysaccharide alginate is one of the most commonly used material for this procedure since it is well tolerated by various tissues, including the brain. two different initial cell concentrations (i.e. 0.5 x10(6)/ml and 1.0 x 10(6)/ml) were tested, in order to identify which one could better reflect the homogeneous cell distribution into the alginate beads and guarantee a good cell viability at different times of culture. as evidenced, the higher number of cells promoted the formation of clusters resulting in a better interaction among encapsulated cells and the subsequent promotion of mitotic activity. the distribution of alive/dead cells into the alginate beads was verified and followed at different time points through the fluorescein diacetate/propidium iodide (FDA/PI) staining, confirming the presence of living neuronal positive cells, as determined from fluorescence microscopy imaging. the functionality of the encapsulated NT2 cells was confirmed by their dopamine production capability as assessed by UV vis spectrophotometric analysis and by liquid chromatography mass spectrometry (LC-MS). The NT2/microspheres system can be considered a groundbreaking experimental procedure, a functionally active platform, able to produce and release dopamine, and thus potentially exploitable for therapy in parkinson's disease
A discrepancy between platelet alpha 2-receptor density and functional circulatory changes in hypertensives
No full textTo investigate whether differences exist in peripheral alpha 2-adrenoceptors between normotensive and hypertensive subjects, we determined platelet alpha 2-adrenoceptor density in 10 (7 males) untreated essential hypertensives (mean age of 51.1 years, range of 44-59 years) and in 10 age- and sex-matched normotensive controls. Moreover, in hypertensive patients, we examined the relationship between receptor density and cardiovascular reactivity to mental arithmetic, static handgrip, and bicycle exercise, to verify the hypothesis that alpha 2-adrenoceptors might play a role in modulation of hemodynamic response to sympathetic stimuli. alpha 2-Adrenoceptor density, as calculated by binding of [3H]yohimbine to platelets, was significantly higher in essential hypertensives (314.8 +/- 38.7 fmol/mg) than in normotensive subjects (213.6 +/- 34.7 fmol/mg) (p less than 0.05), whereas receptor affinity was similar in both groups (4.0 +/- 0.5 nM hypertensives, 4.3 +/- 0.5 nM normotensives; p greater than 0.05). Mental arithmetic increased mean arterial pressure (MAP) by 21.5% from basal values and heart rate (HR) by 13.2%. During isometric exercise, MAP increased by 38.1% and HR by 24.7%, while during bicycle ergometry, mean increases in MAP and HR from baseline were of 27.2 and 54.3%, respectively. No correlation was found between platelet alpha 2-adrenoceptor density and percent changes in MAP induced by all tests, or between adrenoceptors and absolute basal and peak MAP values. Our findings suggest that in hypertensive patients, peripheral alpha 2-adrenoceptors are increased with respect to matched normotensives, but these receptors seem not to be involved in the modulation of cardiovascular adaptation to enhanced sympathetic activity
Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies
No full textApoptosis is a form of programmed cell death that results in the orderly and efficient removal of damaged cells, such as those resulting from DNA damage or during development. Apoptosis can be triggered by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as the binding of ligands to cell surface death receptors. Deregulation in apoptotic cell death machinery is an hallmark of cancer. Apoptosis alteration is responsible not only for tumor development and progression but also for tumor resistance to therapies. Most anticancer drugs currently used in clinical oncology exploit the intact apoptotic signaling pathways to trigger cancer cell death. Thus, defects in the death pathways may result in drug resistance so limiting the efficacy of therapies. Therefore, a better understanding of the apoptotic cell death signaling pathways may improve the efficacy of cancer therapy and bypass resistance. This review will highlight the role of the fundamental regulators of apoptosis and how their deregulation, including activation of anti-apoptotic factors (i.e., Bcl-2, Bcl-xL, etc) or inactivation of pro-apoptotic factors (i.e., p53 pathway) ends up in cancer cell resistance to therapies. In addition, therapeutic strategies aimed at modulating apoptotic activity are briefly discussed
Pityriasis lichenoides-like lesions with perifolliculitis in Lyme borreliosis
No full textA 13-year-old girl presented cutaneous lesions reminiscent of pityriasis lichenoides, associated with headache and fever. The clinical features raised the suspicion of Lyme borreliosis due to their occurrence three months after a trip in an endemic area. The diagnosis of Lyme borreliosis was confirmed by the demonstration of spirochete-like bodies inside the lesions with Warthin-Starry silver stain and by identifying B. burgdorferi flagellar genoma in the affected skin with polymerase-chain reaction. The authors discussed the diagnosis, prognosis and therapy of this unique case of Lyme borreliosis
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