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No full textHebb's idea of a cell assembly as the fundamental unit of neural information processing has dominated neuroscience like no other theoretical concept within the past 60 years. A range of different physiological phenomena, from precisely synchronized spiking to broadly simultaneous rate increases, has been subsumed under this term. Yet progress in this area is hampered by the lack of statistical tools that would enable to extract assemblies with arbitrary constellations of time lags, and at multiple temporal scales, partly due to the severe computational burden. Here we present such a unifying methodological and conceptual framework which detects assembly structure at many different time scales, levels of precision, and with arbitrary internal organization. Applying this methodology to multiple single unit recordings from various cortical areas, we find that there is no universal cortical coding scheme, but that assembly structure and precision significantly depends on the brain area recorded and ongoing task demands
Chitosan and Chitosan derivative nanoparticles bearing cisplatin complexed with polycarboxylate polymer
No full textCisplatin, a widely used antineoplastic drug, presents various adverse effects. Cisplatin complexes with polycarboxylate polymers have been proved biologically active, less toxic than Cisplatin and effective in suppressing ovarian tumour growth in vivo. Nanoparticles bearing such complexes could further improve their pharmacological action. Our current work deals with the preparation of nanoparticles via electrostatic interaction between some of the above complexes, which are anionic macromolecules, and chitosan or chitosan derivatives chosen as cationic polyelectrolytes.
The polycarboxylate polymers used to address this aim were sodium alginate (ALGI), Poly-L-glutamic acid sodium salt (PLGLU) and sodium hyaluronate (HA), while the chitosan derivatives were N-trimethyl chitosan (TMC) and N-trimethyl glycol chitosan (TMGC).
In chronological order, the first nanoparticle formulation was prepared using chitosan or TMC with a DDP-ALGI complex. This formulation yielded significant results in terms of particle properties and antitumor activity in vitro. The results of this work were published recently [1].
The investigation was then continued by preparing nanoparticles through the interaction of TMC or TMGC with a DDP-PLGLU complex. Interesting results were obtained with TMC/DDP-PLGLU nanoparticles, which showed cytotoxicity lower than that of TMC/DDP-ALGI nanoparticles. Those made of TMGC and DDP-PLGLU had a low stability at physiological pH (7.4), so this system was not subjected to further investigation.
Finally, we studied the nanoparticles made of TMC and a DDP-HA complex. This formulation showed interesting features allowing the transformation of the negatively charged macromolecular DDP-HA complex into a different system with new properties, such as small size, a positive zeta potential and a good drug loading. In vitro pharmacological experiments indicated that both the complex, obtained under particular experimental conditions, and the nanoparticles yielded promising results for further in vivo studies of their antitumor activity
Cortical free-association dynamics: Distinct phases of a latching network
No full textA Potts associative memory network has been proposed as a simplified model of macroscopic cortical dynamics, in which each Potts unit stands for a patch of cortex, which can be activated in one of S local attractor states. The internal neuronal dynamics of the patch is not described by the model, rather it is subsumed into an effective description in terms of graded Potts units, with adaptation effects both specific to each attractor state and generic to the patch. If each unit, or patch, receives effective (tensor) connections from C other units, the network has been shown to be able to store a large number p of global patterns, or network attractors, each with a fraction a of the units active, where the critical load p_{c} scales roughly like p_{c}≈CS^{2}/aln(1/a) (if the patterns are randomly correlated). Interestingly, after retrieving an externally cued attractor, the network can continue jumping, or latching, from attractor to attractor, driven by adaptation effects. The occurrence and duration of latching dynamics is found through simulations to depend critically on the strength of local attractor states, expressed in the Potts model by a parameter w. Here we describe with simulations and then analytically the boundaries between distinct phases of no latching, of transient and sustained latching, deriving a phase diagram in the plane w-T, where T parametrizes thermal noise effects. Implications for real cortical dynamics are briefly reviewed in the conclusions
Managing diabetic patients with moderate or severe renal impairment using DPP-4 inhibitors: focus on vildagliptin
No full textBACKGROUND:
Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel classified oral anti-diabetic drugs for the treatment of type 2 diabetes mellitus (T2DM) that provide important reduction in glycated hemoglobin, with a low risk for hypoglycemia and no weight gain. In T2DM patients with reduced renal function, adequate glycemic control is essential to delay the progress of kidney dysfunction, but they are at a greater risk of experiencing hypoglycemic events, especially with longer-acting sulfonylureas and meglitinides.
OBJECTIVE:
To evaluate vildagliptin as an option to achieve glycemic control in T2DM patients with moderate or severe chronic kidney disease (CKD).
METHODS:
A comprehensive search in the literature was performed using the term "vildagliptin." Original articles and reviews exploring our topic were carefully selected.
RESULTS:
Vildagliptin provides effective glycemic control in patients with T2DM and CKD. Dose reductions are required for vildagliptin and other DPP-4 inhibitors, except linagliptin, in T2DM patients with moderate-to-severe CKD. Dose of vildagliptin had to be reduced by half (to 50 mg/day) both for moderate (estimated glomerular filtration rate [eGFR] ≥30 to ≤50 mL/min) and severe CKD (eGFR < 30 mL/min). Available results support a favorable efficacy, safety, and tolerability profile for vildagliptin in T2DM with moderate or severe renal failure. Preliminary data may suggest additional benefits beyond improvement of glycemic control.
CONCLUSION:
Vildagliptin can be safely used in T2DM patients with varying degrees of renal impairment. Dose adjustments for renal impairment are required. Potential long-term renal benefit of vildagliptin needs to be further explored
NK cell surveillance of hematological malignancies. Therapeutic implications and regulation by chemokine receptors
No full textNK cells are circulating innate lymphoid cells that constantly move from bloodstream into tissues, exerting several functions including tumor surveillance. For this reason, NK cells are considered attractive target for cancer immunotherapy. Several strategies are employed to harness NK cell efficacy especially in hematological tumors, including adoptive transfer, genetic manipulation to overexpress chimeric antigen receptors and cytokine or immunomodulatory drug treatments of ex-vivo cultivated and expanded NK cells. Several chemokine receptors support NK cell tissue homing and are required for efficient tumor infiltration. Nevertheless, chemokine receptor expression is often insufficient, or their respective ligands may not be expressed in the tumor microenvironment, thus limiting NK cell localization at the tumor site. Therefore, strategies to implement expression or promote the function of the correct chemokine receptor/ligand axes have been employed in the last years with promising results in preclinical models. In this review, we discuss how chemokine receptors and their ligands regulate the trafficking and localization of NK cells in hematological tumors and how the chemokine function can be manipulated to improve current therapeutic approaches
Metodo di produzione di matrici compatte bioadesive impiegabili come tali o per il rilascio controllato di sostanze attive e matrici compatte così ottenute.
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