RGB-02 (biosimilar pegfilgrastim) in the treatment of chemotherapy-induced neutropenia.

Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. The development and use of biosimilar agents help to rationalize healthcare expenditure and improve access to modern therapies to all who need them. This review focuses on pegfilgrastims with important role in oncology supportive care.

Efficacy and safety of RGB-02, a pegfilgrastim biosimilar to prevent chemotherapy-induced neutropenia: results of a randomized, double-blind phase III clinical study vs. reference pegfilgrastim in patients with breast cancer receiving chemotherapy.

Background: Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is accepted standard for prevention of chemotherapy-induced neutropenia. RGB-02 (Gedeon Richter) is a proposed biosimilar to pegylated G-CSF (Neulasta®, Amgen) with sustained release properties. This is a randomized, comparative, double-blind, multicenter study to evaluate efficacy and safety of RGB-02 in breast cancer patients receiving cytotoxic regimen.

Propagation of postsynaptic currents and potentials via gap junctions in GABAergic networks of the rat hippocampus.

The integration of synaptic signalling in the mammalian hippocampus underlies higher cognitive functions such as learning and memory. We have studied the gap junction-mediated cell-to-cell and network propagation of GABA(A) receptor-mediated events in stratum lacunosum moleculare interneurons of the rat hippocampus. Propagated events were identified both in voltage- and current-clamp configurations.

Computational neuropharmacology: dynamical approaches in drug discovery.

Computational approaches that adopt dynamical models are widely accepted in basic and clinical neuroscience research as indispensable tools with which to understand normal and pathological neuronal mechanisms. Although computer-aided techniques have been used in pharmaceutical research (e.g.

Cell type-specific synaptic dynamics of synchronized bursting in the juvenile CA3 rat hippocampus.

Spontaneous synchronous bursting of the CA3 hippocampus in vitro is a widely studied model of physiological and pathological network synchronization. The role of inhibitory conductances during network bursting is not understood in detail, despite the fact that several antiepileptic drugs target GABA(A) receptors. Here, we show that the first manifestation of a burst event is a cell type-specific flurry of GABA(A) receptor-mediated inhibitory input to pyramidal cells, but not to stratum oriens horizontal interneurons.

Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: a network model of the dentate gyrus incorporating cell types and axonal topography.

Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question.

Impact of heterogeneous perisomatic IPSC populations on pyramidal cell firing rates.

Previous computational modeling studies suggested a set of rules underlying the modulation of principal cell firing rates by heterogeneity in the synaptic parameters (peak amplitude and decay kinetics) of populations of GABAergic inputs. Here we performed dynamic clamp experiments in CA1 hippocampal pyramidal cells to test these ideas in biological neurons. In agreement with the simulation studies, the effects of increasing the event-to-event variance in a population of perisomatically injected inhibitory postsynaptic current (IPSC) peak conductances caused either an increase, decrease, or no change in the firing rates of CA1 pyramidal cells depending on the mean around which the scatter was introduced, the degree of the scatter, the depolarization that the pyramidal cell received, and the IPSC reversal potential.

Diversity beyond variance: modulation of firing rates and network coherence by GABAergic subpopulations.

Computational modelling studies have revealed that heterogeneity in interneuronal networks can powerfully modulate firing rates, responses to excitatory inputs, theta-gamma oscillations and network synchrony. In these previous studies, heterogeneity was represented by the degree of variance in various interneuronal synaptic and cellular parameters. However, a major characteristic of gamma-amino-butyric-acid-ergic (GABAergic) synaptic and interneuronal populations is the presence of distinct subgroups, which variance-based approaches cannot fully address.

Increased neuronal firing in computer simulations of sodium channel mutations that cause generalized epilepsy with febrile seizures plus.

Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant familial syndrome with a complex seizure phenotype. It is caused by mutations in one of 3 voltage-gated sodium channel subunit genes (SCN1B, SCN1A, and SCN2A) and the GABA(A) receptor gamma2 subunit gene (GBRG2). The biophysical characterization of 3 mutations (T875M, W1204R, and R1648H) in SCN1A, the gene encoding the CNS voltage-gated sodium channel alpha subunit Na(v)1.

H-channels in epilepsy: new targets for seizure control?

Hyperpolarization-activated cation channels (h-channels) are key regulators of neuronal excitation and inhibition, and have a rich diversity of subunit composition, distribution, modulation and function. Recent results indicate that the behavior of h-channels can be altered significantly by seizures. The activity-dependent, short-term and long-term plasticity of h-channels can, in turn, modulate neuronal excitability.

Postsynaptic effects of GABAergic synaptic diversity: regulation of neuronal excitability by changes in IPSC variance.

GABAergic synaptic inputs to principal cells are heterogeneous in terms of their anatomical, molecular and physiological properties. Whether diversity in GABAergic synaptic inputs affects the efficacy of GABAergic inhibition is not understood. Here we show that alterations in the heterogeneity of IPSC populations arriving at single cells can significantly modify the effects of GABAergic inputs on neuronal excitability.